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269 results on '"Terman, Alexei"'

19. Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system

Author

Zheng Lin, Cedazo-Minguez Angel, Hallbeck Martin, Jerhammar Fredrik, Marcusson Jan, and Terman Alexei

Subjects
Alzheimer disease, Amyloid β-protein, Colocalization, Exocytosis, Immunocytochemistry, Lysosomes, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Amyloid beta peptide (Aβ) is the main component of extraneuronal senile plaques typical of Alzheimer’s disease (AD) brains. Although Aβ is produced by normal neurons, it is shown to accumulate in large amounts within neuronal lysosomes in AD. We have recently shown that under normal conditions the majority of Aβ is localized extralysosomally, while oxidative stress significantly increases intralysosomal Aβ content through activation of macroautophagy. It is also suggested that impaired Aβ secretion and resulting intraneuronal increase of Aβ can contribute to AD pathology. However, it is not clear how Aβ is distributed inside normal neurons, and how this distribution is effected when Aβ secretion is inhibited. Methods Using retinoic acid differentiated neuroblastoma cells and neonatal rat cortical neurons, we studied intracellular distribution of Aβ by double immunofluorescence microscopy for Aβ40 or Aβ42 and different organelle markers. In addition, we analysed the effect of tetanus toxin-induced exocytosis inhibition on the intracellular distribution of Aβ. Results Under normal conditions, Aβ was found in the small cytoplasmic granules in both neurites and perikarya. Only minor portion of Aβ was colocalized with trans-Golgi network, Golgi-derived vesicles, early and late endosomes, lysosomes, and synaptic vesicles, while the majority of Aβ granules were not colocalized with any of these structures. Furthermore, treatment of cells with tetanus toxin significantly increased the amount of intracellular Aβ in both perikarya and neurites. Finally, we found that tetanus toxin increased the levels of intralysosomal Aβ although the majority of Aβ still remained extralysosomally. Conclusion Our results indicate that most Aβ is not localized to Golgi-related structures, endosomes, lysosomes secretory vesicles or other organelles, while the suppression of Aβ secretion increases intracellular intra- and extralysosomal Aβ.

Published
2012
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25. A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer

Author

Omazic, Brigitta, primary, Ayoglu, Burcu, additional, Löhr, Matthias, additional, Segersvärd, Ralf, additional, Verbeke, Caroline, additional, Magalhaes, Isabelle, additional, Potacova, Zuzana, additional, Mattsson, Jonas, additional, Terman, Alexei, additional, Ghazi, Sam, additional, Albiin, Nils, additional, Kartalis, Nikolaos, additional, Nilsson, Peter, additional, Poiret, Thomas, additional, Zhenjiang, Liu, additional, Heuchel, Rainer, additional, Schwenk, Jochen M., additional, Permert, Johan, additional, Maeurer, Markus J., additional, and Ringden, Olle, additional

Published
2017
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26. Mitochondria play a central role in apoptosis induced by alpha-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptor-mediated pro-apoptotic signaling

Author

Weber, Tobias, Dalen, Helge, Andrea, Ladislav, Negre-Salvayre, Anne, Auge, Nathalie, Sticha, Martin, Lloret, Ana, Terman, Alexei, Witting, Paul K, Higuchi, Masahiro, Plasilova, Magdalena, Zivny, Jan, Gellert, Nina, Weber, Christian, and Neuzil, Jiri

Subjects
Apoptosis -- Physiological aspects, Antimitotic agents -- Physiological aspects, Antineoplastic agents, Mitochondria -- Physiological aspects, Cellular signal transduction -- Physiological aspects, Biological sciences, Chemistry
Abstract

Research reveals that alpha-tocopheryl succinate strongly induces apoptosis in multiple cell types, which use mitochondrial pathway. Results indicate that the central role of mitochondria in this apoptotic process involves destabilization by reactive oxygen species and activation of multiple caspaces in lymphoma and epithelial cells.

Published
2003

27. Lysosomal iron, iron chelation, and cell death

Author

Terman, Alexei, Kurz, Tino, Terman, Alexei, and Kurz, Tino

Abstract

Significance: Lysosomes are acidic organelles containing more than fifty hydrolases that provide for the degradation of intracellular and endocytosed materials by autophagy and heterophagy, respectively. They digest a variety of macromolecules, as well as all organelles, and their integrity is crucial. As a result of the degradation of iron-containing macromolecules (e.g., ferritin and mitochondrial components) or endocytosed erythrocytes (by macrophages), lysosomes can accumulate large amounts of iron. This iron occurs often as Fe(II) due to the acidic and reducing lysosomal environment. Fe(II) is known to catalyze Fenton reactions, yielding extremely reactive hydroxyl radicals that may jeopardize lysosomal membrane integrity during oxidative stress. This results in the release of hydrolases and redox-active iron into the cytosol with ensuing damage or cell death. Lysosomes play key roles not only in apoptosis and necrosis but also in neurodegeneration, aging, and atherosclerosis. Recent Advances: The damaging effect of intralysosomal iron can be hampered by endogenous or exogenous iron chelators that enter the lysosomal compartment by membrane permeation, endocytosis, or autophagy. Critical Issues: Cellular sensitivity to oxidative stress is enhanced by lysosomal redox-active iron or by lysosomal-targeted copper chelators binding copper (from degradation of copper-containing macromolecules) in redox-active complexes. Probably due to higher copper levels, lysosomes of malignant cells may be specifically sensitized by such chelators. Future Directions: By increasing lysosomal redox-active iron or exposing cells to lysosomal-targeted copper chelators, it should be possible to enhance the sensitivity of cancer cells to radiation-induced oxidative stress or treatment with cytostatics that induce such stress.

Published
2013
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28. Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system.

Author

Zheng, Lin, Cedazo-Minguez, Angel, Hallbeck, Martin, Jerhammar, Fredrik, Marcusson, Jan, Terman, Alexei, Zheng, Lin, Cedazo-Minguez, Angel, Hallbeck, Martin, Jerhammar, Fredrik, Marcusson, Jan, and Terman, Alexei

Abstract

Background Amyloid beta peptide (Aβ) is the main component of extraneuronal senile plaques typical of Alzheimer’s disease (AD) brains. Although Aβ is produced by normal neurons, it is shown to accumulate in large amounts within neuronal lysosomes in AD. We have recently shown that under normal conditions the majority of Aβ is localized extralysosomally, while oxidative stress significantly increases intralysosomal Aβ content through activation of macroautophagy. It is also suggested that impaired Aβ secretion and resulting intraneuronal increase of Aβ can contribute to AD pathology. However, it is not clear how Aβ is distributed inside normal neurons, and how this distribution is effected when Aβ secretion is inhibited. Methods Using retinoic acid differentiated neuroblastoma cells and neonatal rat cortical neurons, we studied intracellular distribution of Aβ by double immunofluorescence microscopy for Aβ40 or Aβ42 and different organelle markers. In addition, we analysed the effect of tetanus toxin-induced exocytosis inhibition on the intracellular distribution of Aβ. Results Under normal conditions, Aβ was found in the small cytoplasmic granules in both neurites and perikarya. Only minor portion of Aβ was colocalized with trans-Golgi network, Golgi-derived vesicles, early and late endosomes, lysosomes, and synaptic vesicles, while the majority of Aβ granules were not colocalized with any of these structures. Furthermore, treatment of cells with tetanus toxin significantly increased the amount of intracellular Aβ in both perikarya and neurites. Finally, we found that tetanus toxin increased the levels of intralysosomal Aβ although the majority of Aβ still remained extralysosomally. Conclusion Our results indicate that most Aβ is not localized to Golgi-related structures, endosomes, lysosomes secretory vesicles or other organelles, while the suppression of Aβ secretion increases intracellular intra- and extralysosomal Aβ.

Published
2012
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29. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Klionsky, Daniel J., Abdalla, Fabio C., Abeliovich, Hagai, Abraham, Robert T., Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A., Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M., Al-Zeer, Munir A., Albert, Matthew L., Albin, Roger L., Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O., Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K., Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Arancia, Giuseppe, Aris, John P., Asanuma, Katsuhiko, Asare, Nana Y. O., Ashida, Hisashi, Askanas, Valerie, Askew, David S., Auberger, Patrick, Baba, Misuzu, Backues, Steven K., Baehrecke, Eric H., Bahr, Ben A., Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A., Bampton, Edward T. W., Banhegyi, Gabor, Bartholomew, Clinton R., Bassham, Diane C., Bast, Robert C. Jr, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Bechet, Daniel M., Begley, Thomas J., Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J., Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sebastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S., Boise, Lawrence H., Bonaldo, Paolo, Boone, David L., Bornhauser, Beat C., Bortoluci, Karina R., Bossis, Ioannis, Bost, Frederic, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michael, Bozhkov, Peter V., Brady, Nathan R., Brancolini, Claudio, Brech, Andreas, Brenman, Jay E., Brennand, Ana, Bresnick, Emery H., Brest, Patrick, Bridges, Dave, Bristol, Molly L., Brookes, Paul S., Brown, Eric J., Brumell, John H., Brunetti-Pierri, Nicola, Brunk, Ulf T., Bulman, Dennis E., Bultman, Scott J., Bultynck, Geert, Burbulla, Lena F., Bursch, Wilfried, Butchar, Jonathan P., Buzgariu, Wanda, Bydlowski, Sergio P., Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B., Carding, Simon R., Cardoso, Sandra M., Carew, Jennifer S., Carlin, Cathleen R., Carmignac, Virginie, Carneiro, Leticia A. M., Carra, Serena, Caruso, Rosario A., Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C., Chan, Edmond Y., Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S.-L., Chen, Wenli, Chen, Xihui, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H. K., Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H., Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V., Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M. K., Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E., Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T., Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R., Clague, Michael J., Clark, Robert S. B., Clarke, Peter G. H., Clarke, Robert, Codogno, Patrice, Coller, Hilary A., Colombo, Maria I., Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R., Coombs, Graham H., Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P., Cregg, James M., Crespo, Jose L., Cronje, Marianne J., Cuervo, Ana Maria, Cullen, Joseph J., Czaja, Mark J., D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M., Davies, Faith E., De Felici, Massimo, de Groot, John F., de Haan, Cornelis A. M., De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M. D., Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jorn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D., Devenish, Rodney J., Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P., Ding, Wen-Xing, Distelhorst, Clark W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C., Dosenko, Victor, Dowling, James J., Doxsey, Stephen, Dreux, Marlene, Drew, Mark E., Duan, Qiuhong, Duchosal, Michel A., Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L., Edinger, Aimee L., Egea, Gustavo, Eichinger, Ludwig, Eissa, N. Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S., Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M., Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farre, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G., Feng, Jian, Feng, Qili, Feng, Youji, Fesus, Laszlo, Feuer, Ralph, Figueiredo-Pereira, Maria E., Fimia, Gian Maria, Fingar, Diane C., Finkbeiner, Steven, Finkel, Toren, Finley, Kim D., Fiorito, Filomena, Fisher, Edward A., Fisher, Paul B., Flajolet, Marc, Florez-McClure, Maria L., Florio, Salvatore, Fon, Edward A., Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H., Fox, Howard S., Franco, Rodrigo, Frankel, Lisa B., Fransen, Marc, Fuentes, Jose M., Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H., Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G., Gao, Fen-Biao, Gao, George F., Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L., Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R., Gegg, Matthew E., Geng, Jiefei, Germain, Marc, Gestwicki, Jason E., Gewirtz, David A., Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M., Giatromanolaki, Alexandra N., Gibson, Spencer B., Gilkerson, Robert W., Ginger, Michael L., Ginsberg, Henry N., Golab, Jakub, Goligorsky, Michael S., Golstein, Pierre, Gomez-Manzano, Candelaria, Goncu, Ebru, Gongora, Celine, Gonzalez, Claudio D., Gonzalez, Ramon, Gonzalez-Estevez, Cristina, Gonzalez-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V., Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A., Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D., Green, Kim N., Gregorc, Ales, Gros, Frederic, Grose, Charles, Grunt, Thomas W., Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M., Gukovskaya, Anna S., Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B., Halayko, Andrew J., Hale, Amber N., Halonen, Sandra K., Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K., Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E., Harper, J. Wade, Harris, Adrian L., Harris, James, Harris, Steven D., Hashimoto, Makoto, Haspel, Jeffrey A., Hayashi, Shin-Ichiro, Hazelhurst, Lori A., He, Congcong, He, You-Wen, Hebert, Marie-Josee, Heidenreich, Kim A., Helfrich, Miep H., Helgason, Gudmundur V., Henske, Elizabeth P., Herman, Brian, Herman, Paul K., Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A., Hocking, Lynne J., Hofman, Paul, Hofmann, Thomas G., Hohfeld, Jorg, Holyoake, Tessa L., Hong, Ming-Huang, Hood, David A., Hotamisligil, Gokhan S., Houwerzijl, Ewout J., Hoyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A., Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B., Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R., Hur, Gang Min, Hurley, James B., Hussain, Sabah N. A., Hussey, Patrick J., Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L., Ip, Nancy Y., Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M., Jaattela, Marja, Jackson, George R., Jackson, William T., Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X., Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jimenez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O., Johansen, Terje, Johnson, Daniel E., Johnson, Gail V. W., Jones, Nicola L., Joseph, Bertrand, Joseph, Suresh K., Joubert, Annie M., Juhasz, Gabor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O., Kampinga, Harm H., Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A., Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G., Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P., Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H., Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H., Khalil, Hany, Kiel, Jan A. K. W., Kiger, Amy A., Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K., Kim, Peter K., Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C., King, Jason S., Kinsella, Timothy J., Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T., Klucken, Jochen, Knecht, Erwin, Ko, Ben C. B., Koch, Jan C., Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I., Kotake, Yaichiro, Koukourakis, Michael I., Kouri Flores, Juan B., Kovacs, Attila L., Kraft, Claudine, Krainc, Dimitri, Kramer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M., Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T., Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R., Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D., Lapaquette, Pierre, Laporte, Jocelyn F., Laszlo, Lajos, Lavandero, Sergio, Lavoie, Josee N., Layfield, Robert, Lazo, Pedro A., Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J., Lee, Alvin J. X., Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A., Leiro, Jose, Lemasters, John J., Lemoine, Antoinette, Lesniak, Maciej S., Lev, Dina, Levenson, Victor V., Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P., Lieberman, Andrew, Lim, Hyunjung J., Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D., Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P., Liton, Paloma B., Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A., Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A., Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, Lopez-Otin, Carlos, Lossi, Laura, Lotze, Michael T., Low, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frederic, Lukacs, Nicholas W., Lund, Anders H., Lynch-Day, Melinda A., Ma, Yong, Macian, Fernando, MacKeigan, Jeff P., Macleod, Kay F., Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V., Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stephen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L., Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J., Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Marino, Guillermo, Markaki, Maria, Marten, Mark R., Martin, Seamus J., Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M., McConkey, David J., McConnell, Melanie J., McDermott, Catherine, McDonald, Christine, McInerney, Gerald M., McKenna, Sharon L., McLaughlin, Bethann, McLean, Pamela J., McMaster, Christopher R., McQuibban, G. Angus, Meijer, Alfred J., Meisler, Miriam H., Melendez, Alicia, Melia, Thomas J., Melino, Gerry, Mena, Maria A., Menendez, Javier A., Menna-Barreto, Rubem F. S., Menon, Manoj B., Menzies, Fiona M., Mercer, Carol A., Merighi, Adalberto, Merry, Diane E., Meschini, Stefania, Meyer, Christian G., Meyer, Thomas F., Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A. M., Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K., Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M., Monteiro, Mervyn J., Moore, Michael N., Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I., Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C., Motyl, Tomasz, Moussa, Charbel E.-H., Muller, Sylke, Muller, Sylviane, Munger, Karl, Munz, Christian, Murphy, Leon O., Murphy, Maureen E., Musaro, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I., Narendra, Derek P., Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T., Nazarko, Taras Y., Nemchenko, Andriy, Netea, Mihai G., Neufeld, Thomas P., Ney, Paul A., Nezis, Ioannis P., Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A., Noda, Takeshi, Noegel, Angelika A., Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nurnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D., Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L., Oliver, F. Javier, Olsen, Laura J., Olsson, Stefan, Opota, Onya, Osborne, Timothy F., Ostrander, Gary K., Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E., Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K., Parys, Jan B., Parzych, Katherine R., Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M., Peng, Jianxin, Perlmutter, David H., Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J., Petersen, Morten, Petrovski, Goran, Phang, James M., Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valerie, Pierron, Gerard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C., Poggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Pous, Christian, Pozuelo-Rubio, Mercedes, Praetorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E., Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W., Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V. Ashutosh, Rathmell, Jeffrey C., Ravikumar, Brinda, Ray, Swapan K., Reed, Bruce H., Reed, John C., Reggiori, Fulvio, Regnier-Vigouroux, Anne, Reichert, Andreas S., Reiners, John J. Jr, Reiter, Russel J., Ren, Jun, Revuelta, Jose L., Rhodes, Christopher J., Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C., Rocchi, Stephane, Rodemann, H. Peter, Rodriguez de Cordoba, Santiago, Rohrer, Barbel, Roninson, Igor B., Rosen, Kirill, Rost-Roszkowska, Magdalena M., Rouis, Mustapha, Rouschop, Kasper M. A., Rovetta, Francesca, Rubin, Brian P., Rubinsztein, David C., Ruckdeschel, Klaus, Rucker, Edmund B. Rd, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M., Ryter, Stefan W., Sabatini, David M., Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M., Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M. J., Sanchez-Alcazar, Jose A., Sanchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklos, Sato, Ken, Sato, Miyuki, Schapira, Anthony H. V., Scharl, Michael, Schatzl, Hermann M., Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E., Schneider-Stock, Regine, Schoenlein, Patricia V., Schorderet, Daniel F., Schuller, Christoph, Schwartz, Gary K., Scorrano, Luca, Sealy, Linda, Seglen, Per O., Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J., Shanmugam, Mala, Shapiro, Irving M., Shaulian, Eitan, Shaw, Reuben J., Shelhamer, James H., Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S., Shore, Gordon C., Sibirny, Andriy A., Sidhu, Stan B., Sikorska, Beata, Silva-Zacarin, Elaine C. M., Simmons, Alison, Simon, Annabella, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A., Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A., Sirko, Agnieszka, Siu, Parco M., Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P., Slack, Ruth S., Smaili, Soraya S., Smith, Duncan R., Soengas, Maria S., Soldati, Thierry, Song, Xueqin, Sood, Anil K., Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A., Spies, Claudia D., Springer, Wolfdieter, Srinivasula, Srinivasa M., Stefanis, Leonidas, Steffan, Joan S., Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T., Sternberg, Cinthya, Stork, Bjorn, Stralfors, Peter, Subauste, Carlos S., Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J. 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Paul, Terada, Lance S., Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B., Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M., Tomino, Yasuhiko, Tonges, Lars, Tooze, Sharon A., Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H., Tsai, Ting-Fen, Tschan, Mario P., Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S., Tyagi, Suresh C., Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K., Vaccaro, Maria I., Valente, Enza Maria, Van den Berghe, Greet, van der Klei, Ida J., van Doorn, Wouter, van Dyk, Linda F., van Egmond, Marjolein, van Grunsven, Leo A., Vandenabeele, Peter, Vandenberghe, Wim P., Vanhorebeek, Ilse, Vaquero, Eva C., Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D., Vila, Miquel, Vindis, Cecile, Viola, Giampietro, Viscomi, Maria Teresa, Voitsekhovskaja, Olga V., von Haefen, Clarissa, Votruba, Marcela, Wada, Keiji, Wade-Martins, Richard, Walker, Cheryl L., Walsh, Craig M., Walter, Jochen, Wan, Xiang-Bo, Wang, Aimin, Wang, Chenguang, Wang, Dawei, Wang, Fan, Wang, Fen, Wang, Guanghui, Wang, Haichao, Wang, Hong-Gang, Wang, Horng-Dar, Wang, Jin, Wang, Ke, Wang, Mei, Wang, Richard C., Wang, Xinglong, Wang, Xuejun, Wang, Ying-Jan, Wang, Yipeng, Wang, Zhen, Wang, Zhigang Charles, Wang, Zhinong, Wansink, Derick G., Ward, Diane M., Watada, Hirotaka, Waters, Sarah L., Webster, Paul, Wei, Lixin, Weihl, Conrad C., Weiss, William A., Welford, Scott M., Wen, Long-Ping, Whitehouse, Caroline A., Whitton, J. 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K., Wyttenbach, Andreas, Xavier, Ramnik J., Xi, Zhijun, Xia, Pu, Xiao, Gengfu, Xie, Zhiping, Xie, Zhonglin, Xu, Da-Zhi, Xu, Jianzhen, Xu, Liang, Xu, Xiaolei, Yamamoto, Ai, Yamamoto, Akitsugu, Yamashina, Shunhei, Yamashita, Michiaki, Yan, Xianghua, Yanagida, Mitsuhiro, Yang, Dun-Sheng, Yang, Elizabeth, Yang, Jin-Ming, Yang, Shi Yu, Yang, Wannian, Yang, Wei Yuan, Yang, Zhifen, Yao, Meng-Chao, Yao, Tso-Pang, Yeganeh, Behzad, Yen, Wei-Lien, Yin, Jia-Jing, Yin, Xiao-Ming, Yoo, Ook-Joon, Yoon, Gyesoon, Yoon, Seung-Yong, Yorimitsu, Tomohiro, Yoshikawa, Yuko, Yoshimori, Tamotsu, Yoshimoto, Kohki, You, Ho Jin, Youle, Richard J., Younes, Anas, Yu, Li, Yu, Long, Yu, Seong-Woon, Yu, Wai Haung, Yuan, Zhi-Min, Yue, Zhenyu, Yun, Cheol-Heui, Yuzaki, Michisuke, Zabirnyk, Olga, Silva-Zacarin, Elaine, Zacks, David, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zakeri, Zahra, Zeh, Herbert J. Rd, Zeitlin, Scott O., Zhang, Hong, Zhang, Hui-Ling, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xu Dong, Zhao, Mantong, Zhao, Yi-Fang, Zhao, Ying, Zhao, Zhizhuang J., Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jurgen, Zuckerbraun, Brian, Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Klionsky, Daniel J., Abdalla, Fabio C., Abeliovich, Hagai, Abraham, Robert T., Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A., Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M., Al-Zeer, Munir A., Albert, Matthew L., Albin, Roger L., Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O., Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K., Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Arancia, Giuseppe, Aris, John P., Asanuma, Katsuhiko, Asare, Nana Y. 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M., Carra, Serena, Caruso, Rosario A., Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C., Chan, Edmond Y., Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S.-L., Chen, Wenli, Chen, Xihui, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H. K., Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H., Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V., Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M. 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D., Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jorn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D., Devenish, Rodney J., Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P., Ding, Wen-Xing, Distelhorst, Clark W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C., Dosenko, Victor, Dowling, James J., Doxsey, Stephen, Dreux, Marlene, Drew, Mark E., Duan, Qiuhong, Duchosal, Michel A., Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L., Edinger, Aimee L., Egea, Gustavo, Eichinger, Ludwig, Eissa, N. 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Wade, Harris, Adrian L., Harris, James, Harris, Steven D., Hashimoto, Makoto, Haspel, Jeffrey A., Hayashi, Shin-Ichiro, Hazelhurst, Lori A., He, Congcong, He, You-Wen, Hebert, Marie-Josee, Heidenreich, Kim A., Helfrich, Miep H., Helgason, Gudmundur V., Henske, Elizabeth P., Herman, Brian, Herman, Paul K., Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A., Hocking, Lynne J., Hofman, Paul, Hofmann, Thomas G., Hohfeld, Jorg, Holyoake, Tessa L., Hong, Ming-Huang, Hood, David A., Hotamisligil, Gokhan S., Houwerzijl, Ewout J., Hoyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A., Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B., Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R., Hur, Gang Min, Hurley, James B., Hussain, Sabah N. A., Hussey, Patrick J., Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L., Ip, Nancy Y., Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M., Jaattela, Marja, Jackson, George R., Jackson, William T., Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X., Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jimenez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O., Johansen, Terje, Johnson, Daniel E., Johnson, Gail V. W., Jones, Nicola L., Joseph, Bertrand, Joseph, Suresh K., Joubert, Annie M., Juhasz, Gabor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O., Kampinga, Harm H., Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A., Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G., Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P., Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H., Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H., Khalil, Hany, Kiel, Jan A. K. 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Abstract

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

Published
2012
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30. Guidelines for the use and interpretation of assays for monitoring autophagy

Author

Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, 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Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, FengFeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van den Berghe, Greet, van der Klei, Ida J, van Doorn, Wouter, van Dyk, Linda F, van Egmond, Marjolein, van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, Miquel, Vindis, Cécile, Viola, Giampietro, Viscomi, Maria Teresa, Voitsekhovskaja, Olga V, von Haefen, Clarissa, Votruba, Marcela, Wada, Keiji, Wade-Martins, Richard, Walker, Cheryl L, Walsh, Craig M, Walter, Jochen, Wan, Xiang-Bo, Wang, Aimin, Wang, Chenguang, Wang, Dawei, Wang, Fan, Wang, Fen, Wang, Guanghui, Wang, Haichao, Wang, Hong-Gang, Wang, Horng-Dar, Wang, Jin, Wang, Ke, Wang, Mei, Wang, Richard C, Wang, Xinglong, Wang, Xuejun, Wang, Ying-Jan, Wang, Yipeng, Wang, Zhen, Wang, Zhigang Charles, Wang, Zhinong, Wansink, Derick G, Ward, Diane M, Watada, Hirotaka, Waters, Sarah L, Webster, Paul, Wei, Lixin, Weihl, Conrad C, Weiss, William A, Welford, Scott M, Wen, Long-Ping, Whitehouse, Caroline A, Whitton, J Lindsay, Whitworth, Alexander J, Wileman, Tom, Wiley, John W, Wilkinson, Simon, Willbold, Dieter, Williams, Roger L, Williamson, Peter R, Wouters, Bradly G, Wu, Chenghan, Wu, Dao-Cheng, Wu, William K K, Wyttenbach, Andreas, Xavier, Ramnik J, Xi, Zhijun, Xia, Pu, Xiao, Gengfu, Xie, Zhiping, Xie, Zhonglin, Xu, Da-zhi, Xu, Jianzhen, Xu, Liang, Xu, Xiaolei, Yamamoto, Ai, Yamamoto, Akitsugu, Yamashina, Shunhei, Yamashita, Michiaki, Yan, Xianghua, Yanagida, Mitsuhiro, Yang, Dun-Sheng, Yang, Elizabeth, Yang, Jin-Ming, Yang, Shi Yu, Yang, Wannian, Yang, Wei Yuan, Yang, Zhifen, Yao, Meng-Chao, Yao, Tso-Pang, Yeganeh, Behzad, Yen, Wei-Lien, Yin, Jia-jing, Yin, Xiao-Ming, Yoo, Ook-Joon, Yoon, Gyesoon, Yoon, Seung-Yong, Yorimitsu, Tomohiro, Yoshikawa, Yuko, Yoshimori, Tamotsu, Yoshimoto, Kohki, You, Ho Jin, Youle, Richard J, Younes, Anas, Yu, Li, Yu, Long, Yu, Seong-Woon, Yu, Wai Haung, Yuan, Zhi-Min, Yue, Zhenyu, Yun, Cheol-Heui, Yuzaki, Michisuke, Zabirnyk, Olga, Silva-Zacarin, Elaine, Zacks, David, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zakeri, Zahra, Zeh, Herbert J, Zeitlin, Scott O, Zhang, Hong, Zhang, Hui-Ling, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xu Dong, Zhao, Mantong, Zhao, Yi-Fang, Zhao, Ying, Zhao, Zhizhuang J, Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jürgen, and Zuckerbraun, Brian

Abstract

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

Published
2012
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31. Macroautophagy-generated increase of lysosomal amyloid beta-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells

Author

Zheng, Lin, Terman, Alexei, Hallbeck, Martin, Dehvari, Nodi, Cowburn, Richard F., Benedikz, Eirikur, Kagedal, Katarina, Cedazo-Minguez, Angel, Marcusson, Jan, Zheng, Lin, Terman, Alexei, Hallbeck, Martin, Dehvari, Nodi, Cowburn, Richard F., Benedikz, Eirikur, Kagedal, Katarina, Cedazo-Minguez, Angel, and Marcusson, Jan

Abstract

Increasing evidence suggests the toxicity of intracellular amyloid beta-protein (A beta) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 400/c oxygen for five days, and consequent activation of macroautophagy and accumulation of A beta within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as A beta monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular A beta production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of v-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal A beta resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal A beta accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration., authorCount :9

Published
2011
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32. Oxidative Stress and Lysosomes

Author

Kurz, Tino, Brunk, Ulf, Terman, Alexei, Kurz, Tino, Brunk, Ulf, and Terman, Alexei

Abstract

Recent years have witnessed an avalanche of new knowledge implicating free radicals in virtually every aspect of biology and medicine. It is now axiomatic that the regulated accumulation of reactive oxygen species (ROS) contributes to organismal health and well-being and that ROS serve as signaling molecules involved in cell growth, differentiation, gene regulation, replicative senescence and apoptosis. This book is an interdisciplinary text broken up into three consecutive volumes on the biochemistry and cellular/molecular biology of free radicals, transition metals, oxidants and antioxidants, and the role of oxidative stress in human health and disease.

Published
2011

33. Mitochondrial Turnover and Aging of Long-Lived Postmitotic Cells: The Mitochondrial-Lysosomal Axis Theory of Aging

Author

Terman, Alexei, Kurz, Tino, Navratil, Marian, Arriaga, Edgar A, Brunk, Ulf, Terman, Alexei, Kurz, Tino, Navratil, Marian, Arriaga, Edgar A, and Brunk, Ulf

Abstract

It is now generally accepted that aging and eventual death of multicellular organisms is to a large extent related to macromolecular damage by mitochondrially produced reactive oxygen species, mostly affecting long-lived postmitotic cells, such as neurons and cardiac myocytes. These cells are rarely or not at all replaced during life and can be as old as the whole organism. The inherent inability of autophagy and other cellular-degradation mechanisms to remove damaged structures completely results in the progressive accumulation of garbage, including cytosolic protein aggregates, defective mitochondria, and lipofuscin, an intralysosomal indigestible material. In this review, we stress the importance of crosstalk between mitochondria and lysosomes in aging. The slow accumulation of lipofuscin within lysosomes seems to depress autophagy, resulting in reduced turnover of effective mitochondria. The latter not only are functionally deficient but also produce increased amounts of reactive oxygen species, prompting lipofuscinogenesis. Moreover, defective and enlarged mitochondria are poorly autophagocytosed and constitute a growing population of badly functioning organelles that do not fuse and exchange their contents with normal mitochondria. The progress of these changes seems to result in enhanced oxidative stress, decreased ATP production, and collapse of the cellular catabolic machinery, which eventually is incompatible with survival.

Published
2010
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34. Oxidative stress induces macroautophagy of amyloid beta-protein and ensuing apoptosis

Author

Zheng, Lin, Kågedal, Katarina, Dehvari, Nodi, Benedikz, Eirikur, Cowburn, Richard, Marcusson, Jan, Terman, Alexei, Zheng, Lin, Kågedal, Katarina, Dehvari, Nodi, Benedikz, Eirikur, Cowburn, Richard, Marcusson, Jan, and Terman, Alexei

Abstract

There is increasing evidence for the toxicity of intracellular amyloid beta-protein (A beta) to neurons and the involvement of lysosomes in this process in Alzheimer disease (AD). We have recently shown that oxidative stress, a recognized determinant of AD. enhances macroautophagy and leads to intralysosomal accumulation of A beta in Cultured neuroblastoma cells. We hypothesized that oxidative stress promotes AD by stimulating macroautophagy of A that further may induce cell death by destabilizing lysosomal membranes. To investigate such possibility, we compared the effects of hyperoxia (40% ambient oxygen) in cultured HEK293 cells that were transfected with an empty vector (Vector), wild-type APP (APPwt), or Swedish mutant APP (APPswe). Exposure to hyperoxia for 5 days increased the number of cells with A beta-containing lysosomes, as well as the number of apoptotic cells, compared to normoxic conditions. The rate of apoptosis in all three cell lines demonstrated dependence on intralysosomal A beta content (Vector

Published
2009
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35. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Author

Klionsky, Daniel J., Abeliovich, Hagai, Agostinis, Patrizia, Agrawal, Devendra K., Aliev, Giumrakch, S. Askew, David, Baba, Misuzu, H. Baehrecke, Eric, A. Bahr, Ben, Ballabio, Andrea, A. Bamber, Bruce, C. Bassham, Diane, Bergamini, Ettore, Bi, Xiaoning, Biard-Piechaczyk, Martine, S. Blum, Janice, E. Breclesen, Dale, L. Brodsky, Jeffrey, H. Brumell, John, Brunk, Ulf T., Bursch, Wilfried, Camougrand, Nadine, Cebollero, Eduardo, Cecconi, Francesco, Chen, Yingyu, Chin, Lih-Shen, Choi, Augustine, T. Chu, Charleen, Chung, Jongkyeong, G. H. Clarke, Peter, S. B. Clark, Robert, G. Clarke, Steven, Clave, Corinne, L. Cleveland, John, Codogno, Patrice, I. Colombo, Maria, Coto-Montes, Ana, M. Cregg, James, Maria Cuervo, Ana, Debnath, Jayanta, Demarchi, Francesca, B. Dennis, Patrick, A. Dennis, Phillip, Deretic, Vojo, J. Devenish, Rodney, Di Sano, Federica, Fred Dice, J., DiFiglia, Marian, Dinesh-Kumar, Savithramma, W. Distelhorst, Clark, Djavaheri-Mergny, Mojgan, C. Dorsey, Frank, Droege, Wulf, Dron, Michel, A. Jr. Dunn, William, Duszenko, Michael, Tony Eissa, N., Elazar, Zvulun, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Fesues, Laszlo, D. Finley, Kim, M. Fuentes, Jose, Fueyo, Juan, Fujisaki, Kozo, Galliot, Brigitte, Gao, Fen-Biao, A. Gewirtz, David, B. Gibson, Spencer, Gohla, Antje, L. Goldberg, Alfred, Gonzalez, Ramon, Gonzalez-Estevez, Cristina, Gorski, Sharon, A. Gottlieb, Roberta, Haussinger, Dieter, He, You-Wen, Heidenreich, Kim, A. Hill, Joseph, Hoyer-Hansen, Maria, Hu, Xun, Huang, Wei-Pang, Iwasaki, Akiko, Jaattela, Marja, T. Jackson, William, Jiang, Xuejun, Jin, Shengkan, Johansen, Terje, U. Jung, Jae, Kadowaki, Motoni, Kang, Chanhee, Kelekar, Ameeta, H. Kessel, David, A. K. W. Kiel, Jan, Pyo Kim, Hong, Kimchi, Adi, J. Kinsella, Timothy, Kiselyov, Kirill, Kitamoto, Katsuhiko, Knecht, Erwin, Komatsu, Masaaki, Kominami, Eiki, Kondo, Seiji, L. Kovacs, Attila, Kroemer, Guido, Kuan, Chia-Yi, Kumar, Rakesh, Kundu, Mondira, Landry, Jacques, Laporte, Marianne, Le, Weidong, Lei, Huan-Yao, J. Lenardo, Michael, Levine, Beth, Lieberman, Andrew, Lim, Kah-Leong, Lin, Fu-Cheng, Liou, Willisa, F. Liu, Leroy, Lopez-Berestein, Gabriel, Lopez-Otin, Carlos, Lu, Bo, F. Macleod, Kay, Malorni, Walter, Martinet, Wim, Matsuoka, Ken, Mautner, Josef, J. Meijer, Alfred, Melendez, Alicia, Michels, Paul, Miotto, Giovanni, P. Mistiaen, Wilhelm, Mizushima, Noboru, Mograbi, Baharia, Monastyrska, Iryna, N. Moore, Michael, I. Moreira, Paula, Moriyasu, Yuji, Motyl, Tomasz, Muenz, Christian, O. Murphy, Leon, I. Naqvi, Naweed, Neufeld, Thomas, Nishino, Ichizo, A. Nixon, Ralph, Noda, Takeshi, Nuernberg, Bernd, Ogawa, Michinaga, L. Oleinick, Nancy, J. Olsen, Laura, Ozpolat, Bulent, Paglin, Shoshana, E. Palmer, Glen, Papassideri, Issidora, Parkes, Miles, H. Perlmutter, David, Perry, George, Piacentini, Mauro, Pinkas-Kramarski, Ronit, Prescott, Mark, Proikas-Cezanne, Tassula, Raben, Nina, Rami, Abdelhaq, Reggiori, Fulvio, Rohrer, Baerbel, C. Rubinsztein, David, M. Ryan, Kevin, Sadoshima, Junichi, Sakagami, Hiroshi, Sakai, Yasuyoshi, Sandri, Marco, Sasakawa, Chihiro, Sass, Miklos, Schneider, Claudio, O. Seglen, Per, Seleverstov, Oleksandr, Settleman, Jeffre, J. Shacka, John, M. Shapiro, Irving, Sibirny, Andrei, C. M. Silva-Zacarin, Elaine, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, A. Smith, Mark, Spanel-Borowski, Katharina, Srinivas, Vickram, Steeves, Meredith, Stenmark, Harald, E. Stromhaug, Per, S. Subauste, Carlos, Sugimoto, Seiichiro, Sulzer, David, Suzuki, Toshihiko, S. Swanson, Michele, Takeshita, Fumihiko, J. Talbot, Nicholas., Talloczy, Zsolt, Tanaka, Keiji, Tanaka, Kozo, Tanida, Isei, S. Taylor, Graham, Paul Taylor, J., Terman, Alexei, Tettamanti, Gianluca, B. Thompson, Craig, Thumm, Michael, M. Tolkovsky, Aviva, A. Tooze, Sharon, Truant, Ray, V. Tumanovska, Lesya, Uchiyama, Yasuo, Ueno, Takashi, L. Uzcategui, Nestor, van der Klei, Ida, C. Vaquero, Eva, Vellai, Tibor, W. Vogel, Michael, Wang, Hong-Gang, Webster, Paul, W. Wiley, John, Xi, Zhijun, Xiao, Gutian, Yahalom, Joachim, Yang, Jin-Ming, Yap, George, Yin, Xiao-Min, Yoshimori, Tamotsu, Yu, Li, Yue, Zhenyu, Yuzaki, Michisuke, Zabirnyk, Olga, Zheng, Xiaoxiang, Zhu, Xiongwei, L. Deter, Russell, Tabas, Ira, Klionsky, Daniel J., Abeliovich, Hagai, Agostinis, Patrizia, Agrawal, Devendra K., Aliev, Giumrakch, S. Askew, David, Baba, Misuzu, H. Baehrecke, Eric, A. Bahr, Ben, Ballabio, Andrea, A. Bamber, Bruce, C. Bassham, Diane, Bergamini, Ettore, Bi, Xiaoning, Biard-Piechaczyk, Martine, S. Blum, Janice, E. Breclesen, Dale, L. Brodsky, Jeffrey, H. Brumell, John, Brunk, Ulf T., Bursch, Wilfried, Camougrand, Nadine, Cebollero, Eduardo, Cecconi, Francesco, Chen, Yingyu, Chin, Lih-Shen, Choi, Augustine, T. Chu, Charleen, Chung, Jongkyeong, G. H. Clarke, Peter, S. B. Clark, Robert, G. Clarke, Steven, Clave, Corinne, L. Cleveland, John, Codogno, Patrice, I. Colombo, Maria, Coto-Montes, Ana, M. Cregg, James, Maria Cuervo, Ana, Debnath, Jayanta, Demarchi, Francesca, B. Dennis, Patrick, A. Dennis, Phillip, Deretic, Vojo, J. Devenish, Rodney, Di Sano, Federica, Fred Dice, J., DiFiglia, Marian, Dinesh-Kumar, Savithramma, W. Distelhorst, Clark, Djavaheri-Mergny, Mojgan, C. Dorsey, Frank, Droege, Wulf, Dron, Michel, A. Jr. Dunn, William, Duszenko, Michael, Tony Eissa, N., Elazar, Zvulun, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Fesues, Laszlo, D. Finley, Kim, M. Fuentes, Jose, Fueyo, Juan, Fujisaki, Kozo, Galliot, Brigitte, Gao, Fen-Biao, A. Gewirtz, David, B. Gibson, Spencer, Gohla, Antje, L. Goldberg, Alfred, Gonzalez, Ramon, Gonzalez-Estevez, Cristina, Gorski, Sharon, A. Gottlieb, Roberta, Haussinger, Dieter, He, You-Wen, Heidenreich, Kim, A. Hill, Joseph, Hoyer-Hansen, Maria, Hu, Xun, Huang, Wei-Pang, Iwasaki, Akiko, Jaattela, Marja, T. Jackson, William, Jiang, Xuejun, Jin, Shengkan, Johansen, Terje, U. Jung, Jae, Kadowaki, Motoni, Kang, Chanhee, Kelekar, Ameeta, H. Kessel, David, A. K. W. Kiel, Jan, Pyo Kim, Hong, Kimchi, Adi, J. Kinsella, Timothy, Kiselyov, Kirill, Kitamoto, Katsuhiko, Knecht, Erwin, Komatsu, Masaaki, Kominami, Eiki, Kondo, Seiji, L. Kovacs, Attila, Kroemer, Guido, Kuan, Chia-Yi, Kumar, Rakesh, Kundu, Mondira, Landry, Jacques, Laporte, Marianne, Le, Weidong, Lei, Huan-Yao, J. Lenardo, Michael, Levine, Beth, Lieberman, Andrew, Lim, Kah-Leong, Lin, Fu-Cheng, Liou, Willisa, F. Liu, Leroy, Lopez-Berestein, Gabriel, Lopez-Otin, Carlos, Lu, Bo, F. Macleod, Kay, Malorni, Walter, Martinet, Wim, Matsuoka, Ken, Mautner, Josef, J. Meijer, Alfred, Melendez, Alicia, Michels, Paul, Miotto, Giovanni, P. Mistiaen, Wilhelm, Mizushima, Noboru, Mograbi, Baharia, Monastyrska, Iryna, N. Moore, Michael, I. Moreira, Paula, Moriyasu, Yuji, Motyl, Tomasz, Muenz, Christian, O. Murphy, Leon, I. Naqvi, Naweed, Neufeld, Thomas, Nishino, Ichizo, A. Nixon, Ralph, Noda, Takeshi, Nuernberg, Bernd, Ogawa, Michinaga, L. Oleinick, Nancy, J. Olsen, Laura, Ozpolat, Bulent, Paglin, Shoshana, E. Palmer, Glen, Papassideri, Issidora, Parkes, Miles, H. Perlmutter, David, Perry, George, Piacentini, Mauro, Pinkas-Kramarski, Ronit, Prescott, Mark, Proikas-Cezanne, Tassula, Raben, Nina, Rami, Abdelhaq, Reggiori, Fulvio, Rohrer, Baerbel, C. Rubinsztein, David, M. Ryan, Kevin, Sadoshima, Junichi, Sakagami, Hiroshi, Sakai, Yasuyoshi, Sandri, Marco, Sasakawa, Chihiro, Sass, Miklos, Schneider, Claudio, O. Seglen, Per, Seleverstov, Oleksandr, Settleman, Jeffre, J. Shacka, John, M. Shapiro, Irving, Sibirny, Andrei, C. M. Silva-Zacarin, Elaine, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, A. Smith, Mark, Spanel-Borowski, Katharina, Srinivas, Vickram, Steeves, Meredith, Stenmark, Harald, E. Stromhaug, Per, S. Subauste, Carlos, Sugimoto, Seiichiro, Sulzer, David, Suzuki, Toshihiko, S. Swanson, Michele, Takeshita, Fumihiko, J. Talbot, Nicholas., Talloczy, Zsolt, Tanaka, Keiji, Tanaka, Kozo, Tanida, Isei, S. Taylor, Graham, Paul Taylor, J., Terman, Alexei, Tettamanti, Gianluca, B. Thompson, Craig, Thumm, Michael, M. Tolkovsky, Aviva, A. Tooze, Sharon, Truant, Ray, V. Tumanovska, Lesya, Uchiyama, Yasuo, Ueno, Takashi, L. Uzcategui, Nestor, van der Klei, Ida, C. Vaquero, Eva, Vellai, Tibor, W. Vogel, Michael, Wang, Hong-Gang, Webster, Paul, W. Wiley, John, Xi, Zhijun, Xiao, Gutian, Yahalom, Joachim, Yang, Jin-Ming, Yap, George, Yin, Xiao-Min, Yoshimori, Tamotsu, Yu, Li, Yue, Zhenyu, Yuzaki, Michisuke, Zabirnyk, Olga, Zheng, Xiaoxiang, Zhu, Xiongwei, L. Deter, Russell, and Tabas, Ira

Abstract

Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

Published
2008

36. Lysosomes and oxidative stress in aging and apoptosis

Author

Kurz, Tino, Terman, Alexei, Gustafsson, Bertil, Brunk, Ulf, Kurz, Tino, Terman, Alexei, Gustafsson, Bertil, and Brunk, Ulf

Abstract

The lysosomal compartment consists of numerous acidic vesicles (pH ~ 4-5) that constantly fuse and divide. It receives a large number of hydrolases from the trans-Golgi network, while their substrates arrive from both the cell's outside (heterophagy) and inside (autophagy). Many macromolecules under degradation inside lysosomes contain iron that, when released in labile form, makes lysosomes sensitive to oxidative stress. The magnitude of generated lysosomal destabilization determines if reparative autophagy, apoptosis, or necrosis will follow. Apart from being an essential turnover process, autophagy is also a mechanism for cells to repair inflicted damage, and to survive temporary starvation. The inevitable diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow oxidative formation of lipofuscin in long-lived postmitotic cells, where it finally occupies a substantial part of the volume of the lysosomal compartment. This seems to result in a misdirection of lysosomal enzymes away from autophagosomes, resulting in depressed autophagy and the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. This scenario might put aging into the category of autophagy disorders. © 2008 Elsevier B.V. All rights reserved.

Published
2008
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37. Giant mitochondria do not fuse and exchange their contents with normal mitochondria

Author

Navratil, M., Terman, Alexei, Arriaga, E.A., Navratil, M., Terman, Alexei, and Arriaga, E.A.

Abstract

Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giant mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells. © 2007 Elsevier Inc. All rights reserved.

Published
2008
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40. Autophagy, ageing and apoptosis : The role of oxidative stress and lysosomal iron

Author

Kurz, Tino, Terman, Alexei, Brunk, Ulf, Kurz, Tino, Terman, Alexei, and Brunk, Ulf

Abstract

As an outcome of normal autophagic degradation of ferruginous materials, such as ferritin and mitochondrial metalloproteins, the lysosomal compartment is rich in labile iron and, therefore, sensitive to the mild oxidative stress that cells naturally experience because of their constant production of hydrogen peroxide. Diffusion of hydrogen peroxide into the lysosomes results in Fenton-type reactions with the formation of hydroxyl radicals and ensuing peroxidation of lysosomal contents with formation of lipofuscin that amasses in long-lived postmitotic cells. Lipofuscin is a non-degradable polymeric substance that forms at a rate that is inversely related to the average lifespan across species and is built up of aldehyde-linked protein residues. The normal accumulation of lipofuscin in lysosomes seems to reduce autophagic capacity of senescent postmitotic cells-probably because lipofuscin-loaded lysosomes continue to receive newly formed lysosomal enzymes, which results in lack of such enzymes for autophagy. The result is an insufficient and declining rate of autophagic turnover of worn-out and damaged cellular components that consequently accumulate in a way that upsets normal metabolism. In the event of a more substantial oxidative stress, enhanced formation of hydroxyl radicals within lysosomes jeopardizes the membrane stability of particularly iron-rich lysosomes, specifically of autophagolysosomes that have recently participated in the degradation of iron-rich materials. For some time, the rupture of a limited number of lysosomes has been recognized as an early upstream event in many cases of apoptosis, particularly oxidative stress-induced apoptosis, while necrosis results from a major lysosomal break. Consequently, the regulation of the lysosomal content of redox-active iron seems to be essential for the survival of cells both in the short- and the long-term. © 2007 Elsevier Inc. All rights reserved.

Published
2007
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41. Autophagy, organelles and ageing

Author

Terman, Alexei, Gustafsson, Bertil, Brunk, Ulf, Terman, Alexei, Gustafsson, Bertil, and Brunk, Ulf

Abstract

As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological 'garbage' ('waste' materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2007
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42. Autophagy of amyloid beta-protein in differentiated neuroblastoma cells exposed to oxidative stress

Author

Zheng, Lin, Roberg, Karin, Jerhammar, Fredrik, Marcusson, Jan, Terman, Alexei, Zheng, Lin, Roberg, Karin, Jerhammar, Fredrik, Marcusson, Jan, and Terman, Alexei

Abstract

Oxidative stress is considered important for the pathogenesis of Alzheimer disease (AD), which is characterized by the formation of senile plaques rich in amyloid beta-protein (Aβ). Aβ cytotoxicity has been found dependent on lysosomes, which are abundant in AD neurons and are shown to partially co-localize with Aβ. To determine whether oxidative stress has any influence on the relationship between lysosomes and Aβ1-42 (the most toxic form of Aβ), we studied the effect of hyperoxia (40% versus 8% ambient oxygen) on the intracellular localization of Aβ1-42 (assessed by immunocytochemistry) in retinoic acid differentiated SH-SY5Y neuroblastoma cells maintained in serum-free OptiMEM medium. In control cells, Aβ1-42 was mainly localized to small non-lysosomal cytoplasmic granules. Only occasionally Aβ1-42 was found in large (over 1 μm) lysosomal-associated membrane protein 2 positive vacuoles, devoid of the early endosomal marker rab5. These large Aβ1-42-containing lysosomes were not detectable in the presence of serum (known to suppress autophagy), while their number increased dramatically (up to 24-fold) after exposure of cells to hyperoxia during 5 days. Activation of autophagy by hyperoxia was confirmed by transmission electron microscopy. Furthermore, an inhibitor of autophagic sequestration 3-methyladenine prevented the accumulation of Aβ1-42-positive lysosomes due to hyperoxia. In parallel experiments, intralysosomal accumulation of Aβ1-40 following oxidative stress has been found as well. The results suggest that Aβ can be autophagocytosed and its accumulation within neuronal lysosomes is enhanced by oxidative stress. © 2005 Elsevier Ireland Ltd. All rights reserved.

Published
2006
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43. Oxidative stress and Alzheimer disease - The autophagy connection?

Author

Zheng, Lin, Marcusson, Jan, Terman, Alexei, Zheng, Lin, Marcusson, Jan, and Terman, Alexei

Abstract

Intraneuronal accumulation of amyloid beta-protein (A beta) is believed to be responsible for degeneration and apoptosis of neurons and consequent senile plaque formation in Alzheimer disease (AD), the main cause of senile dementia. Oxidative stress, an early determinant of AD, has been recently found to induce intralysosomal A beta accumulation in cultured differentiated neuroblastoma cells through activation of macroautophogy. Because A beta is known to destabilize lysosomal membranes, potentially resulting in apoptotic cell death, this finding suggests the involvement of oxidative stress-induced macroautophagy in the pathogenesis of AD.

Published
2006

44. The lysosomal-mitochondrial axis theory of postmitotic aging and cell death

Author

Terman, Alexei, Gustafsson, Bertil, Brunk, Ulf, Terman, Alexei, Gustafsson, Bertil, and Brunk, Ulf

Abstract

Aging (senescence) is characterized by a progressive accumulation of macromolecular damage, supposedly due to a continuous minor oxidative stress associated with mitochondrial respiration. Aging mainly affects long-lived postmitotic cells, such as neurons and cardiac myocytes, which neither divide and dilute damaged structures, nor are replaced by newly differentiated cells. Because of inherent imperfect lysosomal degradation (autophagy) and other self-repair mechanisms, damaged structures (biological "garbage") progressively accumulate within such cells, both extra- and intralysosomally. Defective mitochondria and aggregated proteins are the most typical forms of extralysosomal "garbage", while lipofuscin that forms due to iron-catalyzed oxidation of autophagocytosed or heterophagocytosed material, represents intralysosomal "garbage". Based on findings that autophagy is diminished in lipofuscin-loaded cells and that cellular lipofuscin content positively correlates with oxidative stress and mitochondrial damage, we have proposed the mitochondrial-lysosomal axis theory of aging, according to which mitochondrial turnover progressively declines with age, resulting in decreased ATP production and increased oxidative damage. Due to autophagy of ferruginous material, lysosomes contain a pool of redox-active iron, which makes these organelles particularly susceptible to oxidative damage. Oxidant-mediated destabilization of lysosomal membranes releases hydrolytic enzymes to the cytosol, eventuating in cell death (either apoptotic or necrotic depending on the magnitude of the insult), while chelation of the intralysosomal pool of redox-active iron prevents these effects. In relation to the onset of oxidant-induced apoptosis, but after the initiating lysosomal rupture, cytochrome c is released from mitochondria and caspases are activated. Mitochondrial damage follows the release of lysosomal hydrolases, which may act either directly or indirectly, through activation of phosp

Published
2006
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45. Mitochondrial damage and intralysosomal degradation in cellular aging

Author

Terman, Alexei, Gustafsson, Bertil, Brunk, Ulf, Terman, Alexei, Gustafsson, Bertil, and Brunk, Ulf

Abstract

Normal mitochondrial respiration is associated with a continuous production of superoxide and hydrogen peroxide, inevitably resulting in minor macromolecular damage. Damaged cellular components are not completely turned over by autophagy and other cellular repair systems, leading to a progressive age-related accumulation of biological "garbage" material, such as defective mitochondria, cytoplasmic protein aggregates and an intralysosomal undegradable material, lipofuscin. These changes primarily affect neurons, cardiac myocytes and other long-lived postmitotic cells that neither dilute this "garbage" by mitotic activity, nor are replaced by newly differentiated cells. Defective mitochondria are insufficient in ATP production and often generate increased amounts of reactive oxygen species, further enhancing oxidative stress. Lipofuscin-loaded lysosomes, in turn, poorly turn over mitochondria that gradually leads to the overload of long-lived postmitotic cells with "garbage" material, decreased adaptability and eventual cell death. © 2006 Elsevier Ltd. All rights reserved.

Published
2006
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46. Oxidative stress, accumulation of biological 'garbage', and aging

Author

Terman, Alexei, Brunk, Ulf, Terman, Alexei, and Brunk, Ulf

Abstract

Normal metabolism is associated with unavoidable mild oxidative stress resulting in biomolecular damage that cannot be totally repaired or removed by cellular degradative systems, including lysosomes, proteasomes, and cytosolic and mitochondrial proteases. Consequently, irreversibly damaged and functionally defective structures (biological 'garbage') accumulate within long-lived postmitotic cells, such as cardiac myocytes and neurons, leading to progressive loss of adaptability and increased probability of death and characterizing a process called aging, or senescence. Intralysosomal 'garbage' is represented by lipofuscin (age pigment), an undegradable autophagocytosed material, while extralysosomal 'garbage' involves oxidatively modified cytosolic proteins, altered biomembranes, defective mitochondria and other organelles. In aged postmitotic cells, heavily lipofuscin-loaded lysosomes perform poorly, resulting in the enhanced accumulation of defective mitochondria, which in turn produce more reactive oxygen species causing additional damage (the mitochondrial- lysosomal axis theory). Potential anti-aging strategies may involve not only overall reduction of oxidative stress, but also the use of intralysosomal iron chelators hampering Fenton-type chemistry as well as the stimulation of cellular degradative systems. © Mary Ann Liebert, Inc.

Published
2006
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47. Lysosomal labilization

Author

Terman, Alexei, Kurz, Tino, Gustafsson, Bertil, Brunk, Ulf, Terman, Alexei, Kurz, Tino, Gustafsson, Bertil, and Brunk, Ulf

Abstract

The lysosomal compartment is the place for cellular degradation of endocytosed and autophagocytosed material and a center for normal turnover of organelles as well as most long-lived proteins. Lysosomes were long considered stable structures that broke and released their many hydrolytic enzymes only following necrotic cell death. It is now realized that lysosomes instead are quite vulnerable, although in a heterogeneous way. Their exposure to a number of events, such as oxidative stress, lysosomotropic detergents and aldhydes, as well as overexpression of the p53 protein, causes time-and-dose-dependent lysosomal rupture that is followed by apoptosis or necrosis. Partial lysosomal rupture has often been found to be an early upstream event in apoptosis, while necrosis results from fulminant lysosomal rupture. Consequently, factors influencing the stability of lysosomes, for instance their content of labile and redox-active iron, seem to be essential for the survival of cells. © 2006 IUBMB.

Published
2006
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48. Autophagy in cardiac myocyte homeostasis, aging, and pathology

Author

Terman, Alexei, Brunk, Ulf, Terman, Alexei, and Brunk, Ulf

Abstract

Autophagy, an intralysosomal degradation of cells' own constituents that includes macro-, micro-, and chaperone-mediated autophagy, plays an important role in the renewal of cardiac myocytes. This cell type is represented by long-lived postmitotic cells with very poor (if any) replacement through differentiation of stem cells. Macroautophagy, the most universal form of autophagy, is responsible for the degradation of various macromolecules and organelles including mitochondria and is activated in response to stress, promoting cell survival. This process is also involved in programmed cell death when injury is irreversible. Even under normal conditions, autophagy is somewhat imperfect, underlying gradual accumulation of defective mitochondria and lipofuscin granules within aging cardiac myocytes. Autophagy is involved in the most important cardiac pathologies including myocardial hypertrophy, cardiomyopathies, and ischemic heart disease, a fact that has led to increasing attention to this process. © 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Published
2005
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49. Autophagy and aging - The importance of maintaining 'clean' cells

Author

Cuervo, Ana Maria, Bergamini, Ettore, Brunk, Ulf, Droge, Wolf, Ffrench, Martine, Terman, Alexei, Cuervo, Ana Maria, Bergamini, Ettore, Brunk, Ulf, Droge, Wolf, Ffrench, Martine, and Terman, Alexei

Abstract

A decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy, macroautophagy and chaperone-mediated outophagy, in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible experimental restorative efforts are discussed.

Published
2005
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50. Guidelines for the use and interpretation of assays for monitoring autophagy

Author

Klionsky, Daniel J., primary, Abdalla, Fabio C., additional, Abeliovich, Hagai, additional, Abraham, Robert T., additional, Acevedo-Arozena, Abraham, additional, Adeli, Khosrow, additional, Agholme, Lotta, additional, Agnello, Maria, additional, Agostinis, Patrizia, additional, Aguirre-Ghiso, Julio A., additional, Ahn, Hyung Jun, additional, Ait-Mohamed, Ouardia, additional, Ait-Si-Ali, Slimane, additional, Akematsu, Takahiko, additional, Akira, Shizuo, additional, Al-Younes, Hesham M., additional, Al-Zeer, Munir A., additional, Albert, Matthew L., additional, Albin, Roger L., additional, Alegre-Abarrategui, Javier, additional, Aleo, Maria Francesca, additional, Alirezaei, Mehrdad, additional, Almasan, Alexandru, additional, Almonte-Becerril, Maylin, additional, Amano, Atsuo, additional, Amaravadi, Ravi K., additional, Amarnath, Shoba, additional, Amer, Amal O., additional, Andrieu-Abadie, Nathalie, additional, Anantharam, Vellareddy, additional, Ann, David K., additional, Anoopkumar-Dukie, Shailendra, additional, Aoki, Hiroshi, additional, Apostolova, Nadezda, additional, Arancia, Giuseppe, additional, Aris, John P., additional, Asanuma, Katsuhiko, additional, Asare, Nana Y.O., additional, Ashida, Hisashi, additional, Askanas, Valerie, additional, Askew, David S., additional, Auberger, Patrick, additional, Baba, Misuzu, additional, Backues, Steven K., additional, Baehrecke, Eric H., additional, Bahr, Ben A., additional, Bai, Xue-Yuan, additional, Bailly, Yannick, additional, Baiocchi, Robert, additional, Baldini, Giulia, additional, Balduini, Walter, additional, Ballabio, Andrea, additional, Bamber, Bruce A., additional, Bampton, Edward T.W., additional, Juhász, Gábor, additional, Bartholomew, Clinton R., additional, Bassham, Diane C., additional, Bast, Robert C., additional, Batoko, Henri, additional, Bay, Boon-Huat, additional, Beau, Isabelle, additional, Béchet, Daniel M., additional, Begley, Thomas J., additional, Behl, Christian, additional, Behrends, Christian, additional, Bekri, Soumeya, additional, Bellaire, Bryan, additional, Bendall, Linda J., additional, Benetti, Luca, additional, Berliocchi, Laura, additional, Bernardi, Henri, additional, Bernassola, Francesca, additional, Besteiro, Sébastien, additional, Bhatia-Kissova, Ingrid, additional, Bi, Xiaoning, additional, Biard-Piechaczyk, Martine, additional, Blum, Janice S., additional, Boise, Lawrence H., additional, Bonaldo, Paolo, additional, Boone, David L., additional, Bornhauser, Beat C., additional, Bortoluci, Karina R., additional, Bossis, Ioannis, additional, Bost, Frédéric, additional, Bourquin, Jean-Pierre, additional, Boya, Patricia, additional, Boyer-Guittaut, Michaël, additional, Bozhkov, Peter V., additional, Brady, Nathan R, additional, Brancolini, Claudio, additional, Brech, Andreas, additional, Brenman, Jay E., additional, Brennand, Ana, additional, Bresnick, Emery H., additional, Brest, Patrick, additional, Bridges, Dave, additional, Bristol, Molly L., additional, Brookes, Paul S., additional, Brown, Eric J., additional, Brumell, John H., additional, Brunetti-Pierri, Nicola, additional, Brunk, Ulf T., additional, Bulman, Dennis E., additional, Bultman, Scott J., additional, Bultynck, Geert, additional, Burbulla, Lena F., additional, Bursch, Wilfried, additional, Butchar, Jonathan P., additional, Buzgariu, Wanda, additional, Bydlowski, Sergio P., additional, Cadwell, Ken, additional, Cahová, Monika, additional, Cai, Dongsheng, additional, Cai, Jiyang, additional, Cai, Qian, additional, Calabretta, Bruno, additional, Calvo-Garrido, Javier, additional, Camougrand, Nadine, additional, Campanella, Michelangelo, additional, Campos-Salinas, Jenny, additional, Candi, Eleonora, additional, Cao, Lizhi, additional, Caplan, Allan B., additional, Carding, Simon R., additional, Cardoso, Sandra M., additional, Carew, Jennifer S., additional, Carlin, Cathleen R., additional, Carmignac, Virginie, additional, Carneiro, Leticia A.M., additional, Carra, Serena, additional, Caruso, Rosario A., additional, Casari, Giorgio, additional, Casas, Caty, additional, Castino, Roberta, additional, Cebollero, Eduardo, additional, Cecconi, Francesco, additional, Celli, Jean, additional, Chaachouay, Hassan, additional, Chae, Han-Jung, additional, Chai, Chee-Yin, additional, Chan, David C., additional, Chan, Edmond Y., additional, Chang, Raymond Chuen-Chung, additional, Che, Chi-Ming, additional, Chen, Ching-Chow, additional, Chen, Guang-Chao, additional, Chen, Guo-Qiang, additional, Chen, Min, additional, Chen, Quan, additional, Chen, Steve S.-L., additional, Chen, WenLi, additional, Chen, Xi, additional, Chen, Xiangmei, additional, Chen, Xiequn, additional, Chen, Ye-Guang, additional, Chen, Yingyu, additional, Chen, Yongqiang, additional, Chen, Yu-Jen, additional, Chen, Zhixiang, additional, Cheng, Alan, additional, Cheng, Christopher H.K., additional, Cheng, Yan, additional, Cheong, Heesun, additional, Cheong, Jae-Ho, additional, Cherry, Sara, additional, Chess-Williams, Russ, additional, Cheung, Zelda H., additional, Chevet, Eric, additional, Chiang, Hui-Ling, additional, Chiarelli, Roberto, additional, Chiba, Tomoki, additional, Chin, Lih-Shen, additional, Chiou, Shih-Hwa, additional, Chisari, Francis V., additional, Cho, Chi Hin, additional, Cho, Dong-Hyung, additional, Choi, Augustine M.K., additional, Choi, DooSeok, additional, Choi, Kyeong Sook, additional, Choi, Mary E., additional, Chouaib, Salem, additional, Choubey, Divaker, additional, Choubey, Vinay, additional, Chu, Charleen T., additional, Chuang, Tsung-Hsien, additional, Chueh, Sheau-Huei, additional, Chun, Taehoon, additional, Chwae, Yong-Joon, additional, Chye, Mee-Len, additional, Ciarcia, Roberto, additional, Ciriolo, Maria R., additional, Clague, Michael J., additional, Clark, Robert S.B., additional, Clarke, Peter G.H., additional, Clarke, Robert, additional, Codogno, Patrice, additional, Coller, Hilary A., additional, Colombo, María I., additional, Comincini, Sergio, additional, Condello, Maria, additional, Condorelli, Fabrizio, additional, Cookson, Mark R., additional, Coombs, Graham H., additional, Coppens, Isabelle, additional, Corbalan, Ramon, additional, Cossart, Pascale, additional, Costelli, Paola, additional, Costes, Safia, additional, Coto-Montes, Ana, additional, Couve, Eduardo, additional, Coxon, Fraser P., additional, Cregg, James M., additional, Crespo, José L., additional, Cronjé, Marianne J., additional, Cuervo, Ana Maria, additional, Cullen, Joseph J., additional, Czaja, Mark J., additional, D'Amelio, Marcello, additional, Darfeuille-Michaud, Arlette, additional, Davids, Lester M., additional, Davies, Faith E., additional, De Felici, Massimo, additional, de Groot, John F., additional, de Haan, Cornelis A.M., additional, De Martino, Luisa, additional, De Milito, Angelo, additional, De Tata, Vincenzo, additional, Debnath, Jayanta, additional, Degterev, Alexei, additional, Dehay, Benjamin, additional, Delbridge, Lea M.D., additional, Demarchi, Francesca, additional, Deng, Yi Zhen, additional, Dengjel, Jörn, additional, Dent, Paul, additional, Denton, Donna, additional, Deretic, Vojo, additional, Desai, Shyamal D., additional, Devenish, Rodney J., additional, Di Gioacchino, Mario, additional, Di Paolo, Gilbert, additional, Di Pietro, Chiara, additional, Díaz-Araya, Guillermo, additional, Díaz-Laviada, Inés, additional, Diaz-Meco, Maria T., additional, Diaz-Nido, Javier, additional, Dikic, Ivan, additional, Dinesh-Kumar, Savithramma P., additional, Ding, Wen-Xing, additional, Distelhorst, Clark W., additional, Diwan, Abhinav, additional, Djavaheri-Mergny, Mojgan, additional, Dokudovskaya, Svetlana, additional, Dong, Zheng, additional, Dorsey, Frank C., additional, Dosenko, Victor, additional, Dowling, James J., additional, Doxsey, Stephen, additional, Dreux, Marlène, additional, Drew, Mark E., additional, Duan, Qiuhong, additional, Duchosal, Michel A., additional, Duff, Karen E., additional, Dugail, Isabelle, additional, Durbeej, Madeleine, additional, Duszenko, Michael, additional, Edelstein, Charles L., additional, Edinger, Aimee L., additional, Egea, Gustavo, additional, Eichinger, Ludwig, additional, Eissa, N. Tony, additional, Ekmekcioglu, Suhendan, additional, El-Deiry, Wafik S., additional, Elazar, Zvulun, additional, Elgendy, Mohamed, additional, Ellerby, Lisa M., additional, Eng, Kai Er, additional, Engelbrecht, Anna-Mart, additional, Engelender, Simone, additional, Erenpreisa, Jekaterina, additional, Escalante, Ricardo, additional, Esclatine, Audrey, additional, Eskelinen, Eeva-Liisa, additional, Espert, Lucile, additional, Espina, Virginia, additional, Fan, Huizhou, additional, Fan, Jia, additional, Fan, Qi-Wen, additional, Fan, Zhen, additional, Fang, Shengyun, additional, Fang, Yongqi, additional, Fanto, Manolis, additional, Fanzani, Alessandro, additional, Farkas, Thomas, additional, Farre, Jean-Claude, additional, Faure, Mathias, additional, Fechheimer, Marcus, additional, Feng, Carl G., additional, Feng, Jian, additional, Feng, Qili, additional, Feng, Youji, additional, Fésüs, László, additional, Feuer, Ralph, additional, Figueiredo-Pereira, Maria E., additional, Fimia, Gian Maria, additional, Fingar, Diane C., additional, Finkbeiner, Steven, additional, Finkel, Toren, additional, Finley, Kim D., additional, Fiorito, Filomena, additional, Fisher, Edward A., additional, Fisher, Paul B., additional, Flajolet, Marc, additional, Florez-McClure, Maria L., additional, Florio, Salvatore, additional, Fon, Edward A., additional, Fornai, Francesco, additional, Fortunato, Franco, additional, Fotedar, Rati, additional, Fowler, Daniel H., additional, Fox, Howard S., additional, Franco, Rodrigo, additional, Frankel, Lisa B., additional, Fransen, Marc, additional, Fuentes, José M., additional, Fueyo, Juan, additional, Fujii, Jun, additional, Fujisaki, Kozo, additional, Fujita, Eriko, additional, Fukuda, Mitsunori, additional, Furukawa, Ruth H., additional, Gaestel, Matthias, additional, Gailly, Philippe, additional, Gajewska, Malgorzata, additional, Galliot, Brigitte, additional, Galy, Vincent, additional, Ganesh, Subramaniam, additional, Ganetzky, Barry, additional, Ganley, Ian G., additional, Gao, Fen-Biao, additional, Gao, George F., additional, Gao, Jinming, additional, Garcia, Lorena, additional, Garcia-Manero, Guillermo, additional, Garcia-Marcos, Mikel, additional, Garmyn, Marjan, additional, Gartel, Andrei L., additional, Gatti, Evelina, additional, Gautel, Mathias, additional, Gawriluk, Thomas R., additional, Gegg, Matthew E., additional, Geng, Jiefei, additional, Germain, Marc, additional, Gestwicki, Jason E., additional, Gewirtz, David A., additional, Ghavami, Saeid, additional, Ghosh, Pradipta, additional, Giammarioli, Anna M., additional, Giatromanolaki, Alexandra N., additional, Gibson, Spencer B., additional, Gilkerson, Robert W., additional, Ginger, Michael L., additional, Ginsberg, Henry N., additional, Golab, Jakub, additional, Goligorsky, Michael S., additional, Golstein, Pierre, additional, Gomez-Manzano, Candelaria, additional, Goncu, Ebru, additional, Gongora, Céline, additional, Gonzalez, Claudio D., additional, Gonzalez, Ramon, additional, González-Estévez, Cristina, additional, González-Polo, Rosa Ana, additional, Gonzalez-Rey, Elena, additional, Gorbunov, Nikolai V., additional, Gorski, Sharon, additional, Goruppi, Sandro, additional, Gottlieb, Roberta A., additional, Gozuacik, Devrim, additional, Granato, Giovanna Elvira, additional, Grant, Gary D., additional, Green, Kim N., additional, Gregorc, Ales, additional, Gros, Frédéric, additional, Grose, Charles, additional, Grunt, Thomas W., additional, Gual, Philippe, additional, Guan, Jun-Lin, additional, Guan, Kun-Liang, additional, Guichard, Sylvie M., additional, Gukovskaya, Anna S., additional, Gukovsky, Ilya, additional, Gunst, Jan, additional, Gustafsson, Åsa B., additional, Halayko, Andrew J., additional, Hale, Amber N., additional, Halonen, Sandra K., additional, Hamasaki, Maho, additional, Han, Feng, additional, Han, Ting, additional, Hancock, Michael K., additional, Hansen, Malene, additional, Harada, Hisashi, additional, Harada, Masaru, additional, Hardt, Stefan E., additional, Harper, J. Wade, additional, Harris, Adrian L., additional, Harris, James, additional, Harris, Steven D., additional, Hashimoto, Makoto, additional, Haspel, Jeffrey A., additional, Hayashi, Shin-ichiro, additional, Hazelhurst, Lori A., additional, He, Congcong, additional, He, You-Wen, additional, Hébert, Marie-Josée, additional, Heidenreich, Kim A., additional, Helfrich, Miep H., additional, Helgason, Gudmundur V., additional, Henske, Elizabeth P., additional, Herman, Brian, additional, Herman, Paul K., additional, Hetz, Claudio, additional, Hilfiker, Sabine, additional, Hill, Joseph A., additional, Hocking, Lynne J., additional, Hofman, Paul, additional, Hofmann, Thomas G., additional, Höhfeld, Jörg, additional, Holyoake, Tessa L., additional, Hong, Ming-Huang, additional, Hood, David A., additional, Hotamisligil, Gökhan S., additional, Houwerzijl, Ewout J., additional, Høyer-Hansen, Maria, additional, Hu, Bingren, additional, Hu, Chien-an A., additional, Hu, Hong-Ming, additional, Hua, Ya, additional, Huang, Canhua, additional, Huang, Ju, additional, Huang, Shengbing, additional, Huang, Wei-Pang, additional, Huber, Tobias B., additional, Huh, Won-Ki, additional, Hung, Tai-Ho, additional, Hupp, Ted R., additional, Hur, Gang Min, additional, Hurley, James B., additional, Hussain, Sabah N.A., additional, Hussey, Patrick J., additional, Hwang, Jung Jin, additional, Hwang, Seungmin, additional, Ichihara, Atsuhiro, additional, Ilkhanizadeh, Shirin, additional, Inoki, Ken, additional, Into, Takeshi, additional, Iovane, Valentina, additional, Iovanna, Juan L., additional, Ip, Nancy Y., additional, Isaka, Yoshitaka, additional, Ishida, Hiroyuki, additional, Isidoro, Ciro, additional, Isobe, Ken-ichi, additional, Iwasaki, Akiko, additional, Izquierdo, Marta, additional, Izumi, Yotaro, additional, Jaakkola, Panu M., additional, Jäättelä, Marja, additional, Jackson, George R., additional, Jackson, William T., additional, Janji, Bassam, additional, Jendrach, Marina, additional, Jeon, Ju-Hong, additional, Jeung, Eui-Bae, additional, Jiang, Hong, additional, Jiang, Hongchi, additional, Jiang, Jean X., additional, Jiang, Ming, additional, Jiang, Qing, additional, Jiang, Xuejun, additional, Jiménez, Alberto, additional, Jin, Meiyan, additional, Jin, Shengkan V., additional, Joe, Cheol O., additional, Johansen, Terje, additional, Johnson, Daniel E., additional, Johnson, Gail V.W., additional, Jones, Nicola L., additional, Joseph, Bertrand, additional, Joseph, Suresh K., additional, Joubert, Annie M., additional, Juillerat-Jeanneret, Lucienne, additional, Jung, Chang Hwa, additional, Jung, Yong-Keun, additional, Kaarniranta, Kai, additional, Kaasik, Allen, additional, Kabuta, Tomohiro, additional, Kadowaki, Motoni, additional, Kågedal, Katarina, additional, Kamada, Yoshiaki, additional, Kaminskyy, Vitaliy O., additional, Kampinga, Harm H., additional, Kanamori, Hiromitsu, additional, Kang, Chanhee, additional, Kang, Khong Bee, additional, Kang, Kwang Il, additional, Kang, Rui, additional, Kang, Yoon-A, additional, Kanki, Tomotake, additional, Kanneganti, Thirumala-Devi, additional, Kanno, Haruo, additional, Kanthasamy, Anumantha G., additional, Kanthasamy, Arthi, additional, Karantza, Vassiliki, additional, Kaushal, Gur P., additional, Kaushik, Susmita, additional, Kawazoe, Yoshinori, additional, Ke, Po-Yuan, additional, Kehrl, John H., additional, Kelekar, Ameeta, additional, Kerkhoff, Claus, additional, Kessel, David H., additional, Khalil, Hany, additional, Kiel, Jan A.K.W., additional, Kiger, Amy A., additional, Kihara, Akio, additional, Kim, Deok Ryong, additional, Kim, Do-Hyung, additional, Kim, Dong-Hou, additional, Kim, Eun-Kyoung, additional, Kim, Hyung-Ryong, additional, Kim, Jae-Sung, additional, Kim, Jeong Hun, additional, Kim, Jin Cheon, additional, Kim, John K., additional, Kim, Peter K., additional, Kim, Seong Who, additional, Kim, Yong-Sun, additional, Kim, Yonghyun, additional, Kimchi, Adi, additional, Kimmelman, Alec C., additional, King, Jason S., additional, Kinsella, Timothy J., additional, Kirkin, Vladimir, additional, Kirshenbaum, Lorrie A., additional, Kitamoto, Katsuhiko, additional, Kitazato, Kaio, additional, Klein, Ludger, additional, Klimecki, Walter T., additional, Klucken, Jochen, additional, Knecht, Erwin, additional, Ko, Ben C.B., additional, Koch, Jan C., additional, Koga, Hiroshi, additional, Koh, Jae-Young, additional, Koh, Young Ho, additional, Koike, Masato, additional, Komatsu, Masaaki, additional, Kominami, Eiki, additional, Kong, Hee Jeong, additional, Kong, Wei-Jia, additional, Korolchuk, Viktor I., additional, Kotake, Yaichiro, additional, Koukourakis, Michael I., additional, Flores, Juan B. Kouri, additional, Kovács, Attila L., additional, Kraft, Claudine, additional, Krainc, Dimitri, additional, Krämer, Helmut, additional, Kretz-Remy, Carole, additional, Krichevsky, Anna M., additional, Kroemer, Guido, additional, Krüger, Rejko, additional, Krut, Oleg, additional, Ktistakis, Nicholas T., additional, Kuan, Chia-Yi, additional, Kucharczyk, Roza, additional, Kumar, Ashok, additional, Kumar, Raj, additional, Kumar, Sharad, additional, Kundu, Mondira, additional, Kung, Hsing-Jien, additional, Kurz, Tino, additional, Kwon, Ho Jeong, additional, La Spada, Albert R., additional, Lafont, Frank, additional, Lamark, Trond, additional, Landry, Jacques, additional, Lane, Jon D., additional, Lapaquette, Pierre, additional, Laporte, Jocelyn F., additional, László, Lajos, additional, Lavandero, Sergio, additional, Lavoie, Josée N., additional, Layfield, Robert, additional, Lazo, Pedro A., additional, Le, Weidong, additional, Le Cam, Laurent, additional, Ledbetter, Daniel J., additional, Lee, Alvin J.X., additional, Lee, Byung-Wan, additional, Lee, Gyun Min, additional, Lee, Jongdae, additional, lee, Ju-hyun, additional, Lee, Michael, additional, Lee, Myung-Shik, additional, Lee, Sug Hyung, additional, Leeuwenburgh, Christiaan, additional, Legembre, Patrick, additional, Legouis, Renaud, additional, Lehmann, Michael, additional, Lei, Huan-Yao, additional, Lei, Qun-Ying, additional, Leib, David A., additional, Leiro, José, additional, Lemasters, John J., additional, Lemoine, Antoinette, additional, Lesniak, Maciej S., additional, Lev, Dina, additional, Levenson, Victor V., additional, Levine, Beth, additional, Levy, Efrat, additional, Li, Faqiang, additional, Li, Jun-Lin, additional, Li, Lian, additional, Li, Sheng, additional, Li, Weijie, additional, Li, Xue-Jun, additional, Li, Yan-Bo, additional, Li, Yi-Ping, additional, Liang, Chengyu, additional, Liang, Qiangrong, additional, Liao, Yung-Feng, additional, Liberski, Pawel P., additional, Lieberman, Andrew, additional, Lim, Hyunjung J., additional, Lim, Kah-Leong, additional, Lim, Kyu, additional, Lin, Chiou-Feng, additional, Lin, Fu-Cheng, additional, Lin, Jian, additional, Lin, Jiandie D., additional, Lin, Kui, additional, Lin, Wan-Wan, additional, Lin, Weei-Chin, additional, Lin, Yi-Ling, additional, Linden, Rafael, additional, Lingor, Paul, additional, Lippincott-Schwartz, Jennifer, additional, Lisanti, Michael P., additional, Liton, Paloma B., additional, Liu, Bo, additional, Liu, Chun-Feng, additional, Liu, Kaiyu, additional, Liu, Leyuan, additional, Liu, Qiong A., additional, Liu, Wei, additional, Liu, Young-Chau, additional, Liu, Yule, additional, Lockshin, Richard A., additional, Lok, Chun-Nam, additional, Lonial, Sagar, additional, Loos, Benjamin, additional, Lopez-Berestein, Gabriel, additional, López-Otín, Carlos, additional, Lossi, Laura, additional, Lotze, Michael T., additional, Low, Peter, additional, Lu, Binfeng, additional, Lu, Bingwei, additional, Lu, Bo, additional, Lu, Zhen, additional, Luciano, Fréderic, additional, Lukacs, Nicholas W., additional, Lund, Anders H., additional, Lynch-Day, Melinda A., additional, Ma, Yong, additional, Macian, Fernando, additional, MacKeigan, Jeff P., additional, Macleod, Kay F., additional, Madeo, Frank, additional, Maiuri, Luigi, additional, Maiuri, Maria Chiara, additional, Malagoli, Davide, additional, Malicdan, May Christine V., additional, Malorni, Walter, additional, Man, Na, additional, Mandelkow, Eva-Maria, additional, Manon, Stephen, additional, Manov, Irena, additional, Mao, Kai, additional, Mao, Xiang, additional, Mao, Zixu, additional, Marambaud, Philippe, additional, Marazziti, Daniela, additional, Marcel, Yves L., additional, Marchbank, Katie, additional, Marchetti, Piero, additional, Marciniak, Stefan J., additional, Marcondes, Mateus, additional, Mardi, Mohsen, additional, Marfe, Gabriella, additional, Mariño, Guillermo, additional, Markaki, Maria, additional, Marten, Mark R., additional, Martin, Seamus J., additional, Martinand-Mari, Camille, additional, Martinet, Wim, additional, Martinez-Vicente, Marta, additional, Masini, Matilde, additional, Matarrese, Paola, additional, Matsuo, Saburo, additional, Matteoni, Raffaele, additional, Mayer, Andreas, additional, Mazure, Nathalie M., additional, McConkey, David J., additional, McConnell, Melanie J., additional, McDermott, Catherine, additional, McDonald, Christine, additional, McInerney, Gerald M., additional, McKenna, Sharon L., additional, McLaughlin, BethAnn, additional, McLean, Pamela J., additional, McMaster, Christopher R., additional, McQuibban, G. Angus, additional, Meijer, Alfred J., additional, Meisler, Miriam H., additional, Meléndez, Alicia, additional, Melia, Thomas J., additional, Melino, Gerry, additional, Mena, Maria A., additional, Menendez, Javier A., additional, Menna-Barreto, Rubem F. S., additional, Menon, Manoj B., additional, Menzies, Fiona M., additional, Mercer, Carol A., additional, Merighi, Adalberto, additional, Merry, Diane E., additional, Meschini, Stefania, additional, Meyer, Christian G., additional, Meyer, Thomas F., additional, Miao, Chao-Yu, additional, Miao, Jun-Ying, additional, Michels, Paul A.M., additional, Michiels, Carine, additional, Mijaljica, Dalibor, additional, Milojkovic, Ana, additional, Minucci, Saverio, additional, Miracco, Clelia, additional, Miranti, Cindy K., additional, Mitroulis, Ioannis, additional, Miyazawa, Keisuke, additional, Mizushima, Noboru, additional, Mograbi, Baharia, additional, Mohseni, Simin, additional, Molero, Xavier, additional, Mollereau, Bertrand, additional, Mollinedo, Faustino, additional, Momoi, Takashi, additional, Monastyrska, Iryna, additional, Monick, Martha M., additional, Monteiro, Mervyn J., additional, Moore, Michael N., additional, Mora, Rodrigo, additional, Moreau, Kevin, additional, Moreira, Paula I., additional, Moriyasu, Yuji, additional, Moscat, Jorge, additional, Mostowy, Serge, additional, Mottram, Jeremy C., additional, Motyl, Tomasz, additional, Moussa, Charbel E.-H., additional, Müller, Sylke, additional, Muller, Sylviane, additional, Münger, Karl, additional, Münz, Christian, additional, Murphy, Leon O., additional, Murphy, Maureen E., additional, Musarò, Antonio, additional, Mysorekar, Indira, additional, Nagata, Eiichiro, additional, Nagata, Kazuhiro, additional, Nahimana, Aimable, additional, Nair, Usha, additional, Nakagawa, Toshiyuki, additional, Nakahira, Kiichi, additional, Nakano, Hiroyasu, additional, Nakatogawa, Hitoshi, additional, Nanjundan, Meera, additional, Naqvi, Naweed I., additional, Narendra, Derek P., additional, Narita, Masashi, additional, Navarro, Miguel, additional, Nawrocki, Steffan T., additional, Nazarko, Taras Y., additional, Nemchenko, Andriy, additional, Netea, Mihai G., additional, Neufeld, Thomas P., additional, Ney, Paul A., additional, Nezis, Ioannis P., additional, Nguyen, Huu Phuc, additional, Nie, Daotai, additional, Nishino, Ichizo, additional, Nislow, Corey, additional, Nixon, Ralph A., additional, Noda, Takeshi, additional, Noegel, Angelika A., additional, Nogalska, Anna, additional, Noguchi, Satoru, additional, Notterpek, Lucia, additional, Novak, Ivana, additional, Nozaki, Tomoyoshi, additional, Nukina, Nobuyuki, additional, Nürnberger, Thorsten, additional, Nyfeler, Beat, additional, Obara, Keisuke, additional, Oberley, Terry D., additional, Oddo, Salvatore, additional, Ogawa, Michinaga, additional, Ohashi, Toya, additional, Okamoto, Koji, additional, Oleinick, Nancy L., additional, Oliver, F. Javier, additional, Olsen, Laura J., additional, Olsson, Stefan, additional, Opota, Onya, additional, Osborne, Timothy F., additional, Ostrander, Gary K., additional, Otsu, Kinya, additional, Ou, Jing-hsiung James, additional, Ouimet, Mireille, additional, Overholtzer, Michael, additional, Ozpolat, Bulent, additional, Paganetti, Paolo, additional, Pagnini, Ugo, additional, Pallet, Nicolas, additional, Palmer, Glen E., additional, Palumbo, Camilla, additional, Pan, Tianhong, additional, Panaretakis, Theocharis, additional, Pandey, Udai Bhan, additional, Papackova, Zuzana, additional, Papassideri, Issidora, additional, Paris, Irmgard, additional, Park, Junsoo, additional, Park, Ohkmae K., additional, Parys, Jan B., additional, Parzych, Katherine R., additional, Patschan, Susann, additional, Patterson, Cam, additional, Pattingre, Sophie, additional, Pawelek, John M., additional, Peng, Jianxin, additional, Perlmutter, David H., additional, Perrotta, Ida, additional, Perry, George, additional, Pervaiz, Shazib, additional, Peter, Matthias, additional, Peters, Godefridus J., additional, Petersen, Morten, additional, Petrovski, Goran, additional, Phang, James M., additional, Piacentini, Mauro, additional, Pierre, Philippe, additional, Pierrefite-Carle, Valérie, additional, Pierron, Gérard, additional, Pinkas-Kramarski, Ronit, additional, Piras, Antonio, additional, Piri, Natik, additional, Platanias, Leonidas C., additional, Pöggeler, Stefanie, additional, Poirot, Marc, additional, Poletti, Angelo, additional, Poüs, Christian, additional, Pozuelo-Rubio, Mercedes, additional, Prætorius-Ibba, Mette, additional, Prasad, Anil, additional, Prescott, Mark, additional, Priault, Muriel, additional, Produit-Zengaffinen, Nathalie, additional, Progulske-Fox, Ann, additional, Proikas-Cezanne, Tassula, additional, Przedborski, Serge, additional, Przyklenk, Karin, additional, Puertollano, Rosa, additional, Puyal, Julien, additional, Qian, Shu-Bing, additional, Qin, Liang, additional, Qin, Zheng-Hong, additional, Quaggin, Susan E., additional, Raben, Nina, additional, Rabinowich, Hannah, additional, Rabkin, Simon W., additional, Rahman, Irfan, additional, Rami, Abdelhaq, additional, Ramm, Georg, additional, Randall, Glenn, additional, Randow, Felix, additional, Rao, V. Ashutosh, additional, Rathmell, Jeffrey C., additional, Ravikumar, Brinda, additional, Ray, Swapan K., additional, Reed, Bruce H., additional, Reed, John C., additional, Reggiori, Fulvio, additional, Régnier-Vigouroux, Anne, additional, Reichert, Andreas S., additional, Reiners, Jr., John J., additional, Reiter, Russel J., additional, Ren, Jun, additional, Revuelta, José L., additional, Rhodes, Christopher J., additional, Ritis, Konstantinos, additional, Rizzo, Elizete, additional, Robbins, Jeffrey, additional, Roberge, Michel, additional, Roca, Hernan, additional, Roccheri, Maria C., additional, Rocchi, Stephane, additional, Rodemann, H. Peter, additional, Rodríguez de Córdoba, Santiago, additional, Rohrer, Bärbel, additional, Roninson, Igor B., additional, Rosen, Kirill, additional, Rost-Roszkowska, Magdalena M., additional, Rouis, Mustapha, additional, Rouschop, Kasper M.A., additional, Rovetta, Francesca, additional, Rubin, Brian P., additional, Rubinsztein, David C., additional, Ruckdeschel, Klaus, additional, Rucker, Edmund B., additional, Rudich, Assaf, additional, Rudolf, Emil, additional, Ruiz-Opazo, Nelson, additional, Russo, Rossella, additional, Rusten, Tor Erik, additional, Ryan, Kevin M., additional, Ryter, Stefan W., additional, Sabatini, David M., additional, Sadoshima, Junichi, additional, Saha, Tapas, additional, Saitoh, Tatsuya, additional, Sakagami, Hiroshi, additional, Sakai, Yasuyoshi, additional, Salekdeh, Ghasem Hoseini, additional, Salomoni, Paolo, additional, Salvaterra, Paul M., additional, Salvesen, Guy, additional, Salvioli, Rosa, additional, Sanchez, Anthony M.J., additional, Sánchez-Alcázar, José A., additional, Sánchez-Prieto, Ricardo, additional, Sandri, Marco, additional, Sankar, Uma, additional, Sansanwal, Poonam, additional, Santambrogio, Laura, additional, Saran, Shweta, additional, Sarkar, Sovan, additional, Sarwal, Minnie, additional, Sasakawa, Chihiro, additional, Sasnauskiene, Ausra, additional, Sass, Miklós, additional, Sato, Ken, additional, Sato, Miyuki, additional, Schapira, Anthony H.V., additional, Scharl, Michael, additional, Schätzl, Hermann M., additional, Scheper, Wiep, additional, Schiaffino, Stefano, additional, Schneider, Claudio, additional, Schneider, Marion E., additional, Schneider-Stock, Regine, additional, Schoenlein, Patricia V., additional, Schorderet, Daniel F., additional, Schüller, Christoph, additional, Schwartz, Gary K., additional, Scorrano, Luca, additional, Sealy, Linda, additional, Seglen, Per O., additional, Segura-Aguilar, Juan, additional, Seiliez, Iban, additional, Seleverstov, Oleksandr, additional, Sell, Christian, additional, Seo, Jong Bok, additional, Separovic, Duska, additional, Setaluri, Vijayasaradhi, additional, Setoguchi, Takao, additional, Settembre, Carmine, additional, Shacka, John J., additional, Shanmugam, Mala, additional, Shapiro, Irving M., additional, Shaulian, Eitan, additional, Shaw, Reuben J., additional, Shelhamer, James H., additional, Shen, Han-Ming, additional, Shen, Wei-Chiang, additional, Sheng, Zu-Hang, additional, Shi, Yang, additional, Shibuya, Kenichi, additional, Shidoji, Yoshihiro, additional, Shieh, Jeng-Jer, additional, Shih, Chwen-Ming, additional, Shimada, Yohta, additional, Shimizu, Shigeomi, additional, Shintani, Takahiro, additional, Shirihai, Orian S., additional, Shore, Gordon C., additional, Sibirny, Andriy A., additional, Sidhu, Stan B., additional, Sikorska, Beata, additional, Silva-Zacarin, Elaine C.M., additional, Simmons, Alison, additional, Simon, Anna Katharina, additional, Simon, Hans-Uwe, additional, Simone, Cristiano, additional, Simonsen, Anne, additional, Sinclair, David A., additional, Singh, Rajat, additional, Sinha, Debasish, additional, Sinicrope, Frank A., additional, Sirko, Agnieszka, additional, Siu, Parco M., additional, Sivridis, Efthimios, additional, Skop, Vojtech, additional, Skulachev, Vladimir P., additional, Slack, Ruth S., additional, Smaili, Soraya S., additional, Smith, Duncan R., additional, Soengas, Maria S., additional, Soldati, Thierry, additional, Song, Xueqin, additional, Sood, Anil K., additional, Soong, Tuck Wah, additional, Sotgia, Federica, additional, Spector, Stephen A., additional, Spies, Claudia D., additional, Springer, Wolfdieter, additional, Srinivasula, Srinivasa M., additional, Stefanis, Leonidas, additional, Steffan, Joan S., additional, Stendel, Ruediger, additional, Stenmark, Harald, additional, Stephanou, Anastasis, additional, Stern, Stephan T., additional, Sternberg, Cinthya, additional, Stork, Björn, additional, Strålfors, Peter, additional, Subauste, Carlos S., additional, Sui, Xinbing, additional, Sulzer, David, additional, Sun, Jiaren, additional, Sun, Shi-Yong, additional, Sun, Zhi-Jun, additional, Sung, Joseph J.Y., additional, Suzuki, Kuninori, additional, Suzuki, Toshihiko, additional, Swanson, Michele S., additional, Swanton, Charles, additional, Sweeney, Sean T., additional, Sy, Lai-King, additional, Szabadkai, György, additional, Tabas, Ira, additional, Taegtmeyer, Heinrich, additional, Tafani, Marco, additional, Takács-Vellai, Krisztina, additional, Takano, Yoshitaka, additional, Takegawa, Kaoru, additional, Takemura, Genzou, additional, Takeshita, Fumihiko, additional, Talbot, Nicholas J., additional, Tan, Kevin S.W., additional, Tanaka, Keiji, additional, Tanaka, Kozo, additional, Tang, Daolin, additional, Tang, Dingzhong, additional, Tanida, Isei, additional, Tannous, Bakhos A., additional, Tavernarakis, Nektarios, additional, Taylor, Graham S., additional, Taylor, Gregory A., additional, Taylor, J. Paul, additional, Terada, Lance S., additional, Terman, Alexei, additional, Tettamanti, Gianluca, additional, Thevissen, Karin, additional, Thompson, Craig B., additional, Thorburn, Andrew, additional, Thumm, Michael, additional, Tian, FengFeng, additional, Tian, Yuan, additional, Tocchini-Valentini, Glauco, additional, Tolkovsky, Aviva M., additional, Tomino, Yasuhiko, additional, Tönges, Lars, additional, Tooze, Sharon A., additional, Tournier, Cathy, additional, Tower, John, additional, Towns, Roberto, additional, Trajkovic, Vladimir, additional, Travassos, Leonardo H., additional, Tsai, Ting-Fen, additional, Tschan, Mario P., additional, Tsubata, Takeshi, additional, Tsung, Allan, additional, Turk, Boris, additional, Turner, Lorianne S., additional, Tyagi, Suresh C., additional, Uchiyama, Yasuo, additional, Ueno, Takashi, additional, Umekawa, Midori, additional, Umemiya-Shirafuji, Rika, additional, Unni, Vivek K., additional, Vaccaro, Maria I., additional, Valente, Enza Maria, additional, Van den Berghe, Greet, additional, van der Klei, Ida J., additional, van Doorn, Wouter G., additional, van Dyk, Linda F., additional, van Egmond, Marjolein, additional, van Grunsven, Leo A., additional, Vandenabeele, Peter, additional, Vandenberghe, Wim P., additional, Vanhorebeek, Ilse, additional, Vaquero, Eva C., additional, Velasco, Guillermo, additional, Vellai, Tibor, additional, Vicencio, José Miguel, additional, Vierstra, Richard D., additional, Vila, Miquel, additional, Vindis, Cécile, additional, Viola, Giampietro, additional, Viscomi, Maria Teresa, additional, Voitsekhovskaja, Olga V., additional, von Haefen, Clarissa, additional, Votruba, Marcela, additional, Wada, Keiji, additional, Wade-Martins, Richard, additional, Walker, Cheryl L., additional, Walsh, Craig M., additional, Walter, Jochen, additional, Wan, Xiang-Bo, additional, Wang, Aimin, additional, Wang, Chenguang, additional, Wang, Dawei, additional, Wang, Fan, additional, Wang, Fen, additional, Wang, Guanghui, additional, Wang, Haichao, additional, Wang, Hong-Gang, additional, Wang, Horng-Dar, additional, Wang, Jin, additional, Wang, Ke, additional, Wang, Mei, additional, Wang, Richard C., additional, Wang, Xinglong, additional, Wang, Xiujie J., additional, Wang, Ying-Jan, additional, Wang, Yipeng, additional, Wang, Zhen-Bo, additional, Wang, Zhigang Charles, additional, Wang, Zhinong, additional, Wansink, Derick G., additional, Ward, Diane M., additional, Watada, Hirotaka, additional, Waters, Sarah L., additional, Webster, Paul, additional, Wei, Lixin, additional, Weihl, Conrad C., additional, Weiss, William A., additional, Welford, Scott M., additional, Wen, Long-Ping, additional, Whitehouse, Caroline A., additional, Whitton, J. 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2012
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