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1. Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis

Author

Matias, Maria I., Yong, Carmen S., Foroushani, Amir, Goldsmith, Chloe, Mongellaz, Cédric, Sezgin, Erdinc, Levental, Kandice R., Talebi, Ali, Perrault, Julie, Rivière, Anais, Dehairs, Jonas, Delos, Océane, Bertand-Michel, Justine, Portais, Jean-Charles, Wong, Madeline, Marie, Julien C., Kelekar, Ameeta, Kinet, Sandrina, Zimmermann, Valérie S., Levental, Ilya, Yvan-Charvet, Laurent, Swinnen, Johannes V., Muljo, Stefan A., Hernandez-Vargas, Hector, Tardito, Saverio, Taylor, Naomi, and Dardalhon, Valérie

Published
2021
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2. Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria.

Author

Guo, Zhijun, Sevrioukova, Irina, Denisov, Ilia, Zhang, Xia, Chiu, Ting-Lan, Thomas, Dafydd, Hanse, Eric, Cuellar, Rebecca, Grinkova, Yelena, Langenfeld, Vanessa, Swedien, Daniel, Stamschror, Justin, Alvarez, Juan, Luna, Fernando, Galván, Adela, Bae, Young, Wulfkuhle, Julia, Gallagher, Rosa, Petricoin, Emanuel, Norris, Beverly, Flory, Craig, Schumacher, Robert, OSullivan, M, Cao, Qing, Chu, Haitao, Lipscomb, John, Atkins, William, Gupta, Kalpna, Kelekar, Ameeta, Blair, Ian, Capdevila, Jorge, Falck, John, Sligar, Stephen, Poulos, Thomas, Georg, Gunda, Ambrose, Elizabeth, and Potter, David

Subjects
CYP3A4, autophagy, biguanide, breast cancer, cytochrome P450, electron transport chain, epoxyeicosatrienoic acid, hexyl-benzyl-biguanide, metformin, mitochondria, AMP-Activated Protein Kinases, Animals, Biguanides, Breast Neoplasms, Catalytic Domain, Cell Respiration, Cytochrome P-450 CYP3A, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Heme, Humans, MCF-7 Cells, Membrane Potential, Mitochondrial, Mice, Mitochondria, Models, Molecular, Protein Transport
Abstract

The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs. Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target. Structure-based design led to discovery of N1-hexyl-N5-benzyl-biguanide (HBB), which bound to the CYP3A4 heme with higher affinity than metformin. HBB potently and specifically inhibited CYP3A4 AA epoxygenase activity. HBB also inhibited growth of established ER+ mammary tumors and suppressed intratumoral mTOR. CYP3A4 AA epoxygenase inhibition by biguanides thus demonstrates convergence between eicosanoid activity in mitochondria and biguanide action in cancer, opening a new avenue for cancer drug discovery.

Published
2017

4. Abstract 44: Hexyl-benzyl-biguanide (HBB) potently and selectively inhibits CYP3A4 epoxygenase activity and inhibits EET stabilization of mitochondrial respiration in ER+HER2- breast cancer cells, inducing glycolysis and pyruvate biosynthesis

Author

Guo, Zhijun, Sevrioukova, Irina, Hanse, Eric, Zhang, Xia, Denisov, Ilia, Chiu, Ting-Lan, Cuellar, Rebecca, Torres, Christian, Wulfkuhle, Julia, Petricoin, Emanuel, Cao, Qing, Chu, Haitao, Norris, Beverly, Schumacher, Robert, Kelekar, Ameeta, Blair, Ian, Capdevila, Jorge, Falck, John, Poulos, Thomas, Sligar, Steven, Georg, Gunda, Amin, Elizabeth, and Potter, David A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Women's Health, Breast Cancer, Cancer, Clinical Research, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Abstract: Cytochrome P450 3A4 (CYP3A4) promotes ER+HER2- breast cancer cell proliferation and survival, in part, by biosynthesis of epoxyeicosatrienoic acids (EETs). EETs are known to regulate mitochondrial function in non-transformed cells, but the roles of CYP3A4 and EETs in regulation of breast cancer bioenergetics are unknown. Hexyl-benzyl-biguanide (HBB) is useful probe of CYP3A4 epoxygenase activity and selectively inhibits EET biosynthesis (IC50 = 9 uM vs. IC50 = 50 uM for CYP2C8). HBB caused depolarization of mitochondria in MCF-7 cells, while (±)-14,15-EET provided partial protection. The soluble epoxide hydrolase (sEH) inhibitor t-AUCB ameliorated inhibition of oxygen consumption rates (OCR) by HBB (20 uM), while there was no effect on extracellular acidification rate (ECAR), indicating that the primary effect of HBB is on OCR. At 30 minutes, HBB added to MCF-7 cells transiently suppressed phosphorylation of pyruvate kinase muscle isozyme 2 (PKM2) on Tyr-105, which has been reported to favor enzymatically inactive dimer over active tetramer. Suppression of phosphorylated PKM2 correlated with subsequent PKM2 tetramer formation and increase of intracellular pyruvate and extracellular lactate at 1 hour. The (±)-14,15-EET regioisomer reduced the pro-glycolytic PKM2 tetramer at 1 hour, suggesting that HBB may promote PKM2 tetramer, in part, through reduction of EET. Prolonged exposure to HBB (20 uM) in cultured cells activated phosphorylation of PKM2 on Tyr-105, but there was increased cellular necrosis correlating with reduced mitochondrial respiration and reduction of ATP stores, indicating that loss of respiration was the dominant effect. HBB inhibited the ER+HER2- MCF-7 xenograft, similar to CYP3A4 silencing. HBB promoted phosphorylation of intratumoral PKM2 on Tyr-105, consistent with long-term exposure to HBB in cultured MCF-7 cells. Notably, MCF-7 tumor response to HBB did not correlate with phosphorylation of AMPK-alpha on Thr-172, a marker of AMPK activation. Metformin (5 mM) exhibited no effect on PKM2 or its phosphorylation in cultured MCF-7 cells. Together, these results indicate that part of the inhibitory effect of HBB on ER+HER2- breast cancer is mediated through inhibition of respiration. Significance: These results establish HBB as a useful chemical probe of respiration, with indirect effects on PKM2 regulation. HBB may also be useful as a potential therapeutic candidate for ER+HER2- breast cancer. Citation Format: Zhijun Guo, Irina Sevrioukova, Eric Hanse, Xia Zhang, Ilia Denisov, Ting-Lan Chiu, Rebecca Cuellar, Christian Torres, Julia Wulfkuhle, Emanuel Petricoin, Qing Cao, Haitao Chu, Beverly Norris, Robert Schumacher, Ameeta Kelekar, Ian Blair, Jorge Capdevila, John Falck, Thomas Poulos, Steven Sligar, Gunda Georg, Elizabeth Amin, David A. Potter. Hexyl-benzyl-biguanide (HBB) potently and selectively inhibits CYP3A4 epoxygenase activity and inhibits EET stabilization of mitochondrial respiration in ER+HER2- breast cancer cells, inducing glycolysis and pyruvate biosynthesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 44.

Published
2016

5. EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection.

Author

Olenchock, Benjamin, Moslehi, Javid, Baik, Alan, Davidson, Shawn, Williams, Jeremy, Gibson, William, Chakraborty, Abhishek, Pierce, Kerry, Miller, Christine, Hanse, Eric, Kelekar, Ameeta, Sullivan, Lucas, Wagers, Amy, Clish, Clary, Vander Heiden, Matthew, and Kaelin, William

Subjects
Animals, Hypoxia-Inducible Factor-Proline Dioxygenases, Ischemia, Ischemic Preconditioning, Ketoglutaric Acids, Kynurenic Acid, Liver, Mice, Models, Animal, Myocardial Reperfusion Injury, Parabiosis
Abstract

Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.

Published
2016

6. Abstract 3568: CYP3A4 epoxygenase activity mediates ER+ mammary tumor growth and angiogenesis, in part, through EET biosynthesis and is inhibited by biguanides

Author

Guo, Zhijun, Sevrioukova, Irina F, Hanse, Eric, Denisov, Ilia, Zhang, Xia, Chiu, Ting-Lan, Swedien, Daniel, Stamschror, Justin, Alvarez, Juan, Ortiz, William Marerro, Morgan, Monique, Maher, Michael, Chavez, Kathryn J, Thomas, Dafydd, Bae, Young Kyung, Henriksen, Jonathan, Norris, Beverly, Schumacher, Robert J, Wang, Henry, Bliss, Robin, Chu, Haitao, Cuellar, Rebecca, Poulos, Thomas L, Sligar, Stephen G, Atkins, William, Schmechel, Stephen, Capdevila, Jorge, Falck, John, Blair, Ian, Jones, Jeffrey P, Georg, Gunda, Gupta, Kalpna, Kelekar, Ameeta, Amin, Elizabeth, and Potter, David A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Breast Cancer, Cancer, Women's Health, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Abstract: While cytochrome P450 enzymes (CYPs) are implicated in tumor angiogenesis through biosynthesis of epoxyeicosatrienoic acids (EETs), little is known about breast cancer cell-intrinsic CYPs that exhibit epoxygenase activity, such as CYP3A4. In an orthotopic breast cancer model, silencing of epithelial CYP3A4 suppressed angiogenesis-related escape of ER+ breast tumors from dormancy. While the diabetes drug metformin inhibits mitochondrial complex I and inhibits tumor growth, how it does so is unknown. Metformin inhibited CYP epoxygenase activity and co-crystallized in the active site of CYP3A4, hydrogen bonding with arginine 212, allowing the development of hexyl-benzyl-biguanide (HBB) as a CYP3A4 inhibitor using molecular modeling. HBB exhibited more than 10-fold greater potency than metformin for inhibition of ER+ mammary tumor growth and inhibited associated tumor angiogenesis. HBB inhibited EET biosynthesis ∼40-fold more potently than metformin and was ∼40-fold more potent for activation of AMPK phosphorylation. EETs suppressed and CYP silencing promoted AMPK phosphorylation, linking CYPs with AMPK regulation in breast cancer. HBB depolarized mitochondria, reduced oxygen consumption rates and suppressed the Warburg effect, while EETs restored the mitochondrial membrane potential. CYP3A4 silencing and HBB treatment increased reactive oxygen species (ROS) production, suggesting that CYPs suppress cancer cell death, in part, through suppression of ROS. CYP3A4 silencing sensitized breast cancer cells to hormonal therapy and chemotherapy, abrogated by EETs. Because EETs are autocrine, paracrine and endocrine, these results implicate CYPs in tumor growth, in part, through cell-cell mediation of mitochondrial homeostasis and demonstrate the potential of CYP3A4 as a therapeutic target in breast cancer. Citation Format: Zhijun Guo, Irina F. Sevrioukova, Eric Hanse, Ilia Denisov, Xia Zhang, Ting-Lan Chiu, Daniel Swedien, Justin Stamschror, Juan Alvarez, William Marerro Ortiz, Monique Morgan, Michael Maher, Kathryn J. Chavez, Dafydd Thomas, Young Kyung Bae, Jonathan Henriksen, Beverly Norris, Robert J. Schumacher, Henry Wang, Robin Bliss, Haitao Chu, Rebecca Cuellar, Thomas L. Poulos, Stephen G. Sligar, William Atkins, Stephen Schmechel, Jorge Capdevila, John Falck, Ian Blair, Jeffrey P. Jones, Gunda Georg, Kalpna Gupta, Ameeta Kelekar, Elizabeth Amin, David A. Potter. CYP3A4 epoxygenase activity mediates ER+ mammary tumor growth and angiogenesis, in part, through EET biosynthesis and is inhibited by biguanides. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3568. doi:10.1158/1538-7445.AM2015-3568

Published
2015

8. Abstract 2689: Breast cancer inhibition by a novel and potent biguanide, N1-hexyl-N5-benzyl-biguanide

Author

Guo, Zhijun, Chavez, Kathryn J, Alvarez, Juan, Zhang, Xia, Norris, Beverly, Maher, Michael, Morgan, Monique, Schumacher, Robert J, Cuellar, Rebecca, Sevrioukova, Irina F, Poulos, Thomas L, Denisov, Ilia, Sligar, Stephen G, Gupta, Kalpna, Blair, Ian A, Capdevila, Jorge, Kelekar, Ameeta, Amin, Elizabeth, Georg, Gunda, and Potter, David A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Orphan Drug, Rare Diseases, Prevention, Breast Cancer, Women's Health, Cancer, 5.1 Pharmaceuticals, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Abstract: Metformin is a widely used biguanide diabetes drug that is associated with decreased breast cancer risk and is currently being studied for treatment and prevention of breast cancer. While metformin and biguanides buformin and phenformin exhibit inhibitory activity against breast cancer in vitro and in vivo, they lack potency (IC50=5-20 mM) and their mechanisms of action remain unclear. More potent biguanides may provide insights into biguanide anti-cancer activity and we therefore studied the novel biguanide N1-hexyl-N5-benzyl-biguanide mesylate (HBB), which potently inhibits the MCF-7 and MDA-MB-231 breast cancer lines (IC50=20 uM for both lines). HBB induces AMPK phosphorylation in both lines at 10 uM concentration, whereas similarly dosed metformin, buformin or phenformin exhibits no activity. HBB also inhibits STAT3 phosphorylation at 10 uM concentration, whereas metformin dosed at 10 uM exhibits no activity. HBB reduced the mitochondrial membrane potential of both lines, but the effect was more prominent in the MDA-MB-231 line. HBB also induced ROS within 2.5 hours of exposure in the MCF-7 and MDA-MB-231 lines and caused rapid necrosis, but not apoptosis. N-acetylcysteine provides partial protection from HBB for MDA-231 line, but not the MCF-7 line. HBB provides proof of principle that highly potent biguanides can be synthesized with at least 250-fold greater potency than metformin, which can provide insights into the cancer inhibitory mechanisms of biguanide drugs. R01 CA113570, Randy Shaver Foundation, CTSI University of Minnesota Citation Format: Zhijun Guo, Kathryn J. Chavez, Juan Alvarez, Xia Zhang, Beverly Norris, Michael Maher, Monique Morgan, Robert J. Schumacher, Rebecca Cuellar, Irina F. Sevrioukova, Thomas L. Poulos, Ilia Denisov, Stephen G. Sligar, Kalpna Gupta, Ian A. Blair, Jorge Capdevila, Ameeta Kelekar, Elizabeth Amin, Gunda Georg, David A. Potter. Breast cancer inhibition by a novel and potent biguanide, N1-hexyl-N5-benzyl-biguanide. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2689. doi:10.1158/1538-7445.AM2014-2689

Published
2014

9. The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease

Author

McDonald-Hyman, Cameron, Muller, James T., Loschi, Michael, Thangavelu, Govindarajan, Saha, Asim, Kumari, Sudha, Reichenbach, Dawn K., Smith, Michelle J., Zhang, Guoan, Koehn, Brent H., Lin, Jiqiang, Mitchell, Jason S., Fife, Brian T., Panoskaltsis-Mortari, Angela, Feser, Colby J., Kirchmeier, Andrew Kemal, Osborn, Mark J., Hippen, Keli L., Kelekar, Ameeta, Serody, Jonathan S., Turka, Laurence A., Munn, David H., Chi, Hongbo, Neubert, Thomas A., Dustin, Michael L., and Blazar, Bruce R.

Subjects
Cytoskeletal proteins -- Health aspects, Graft vs. host disease -- Development and progression -- Care and treatment -- Genetic aspects, Immune response -- Genetic aspects, T cells -- Health aspects -- Genetic aspects, Health care industry
Abstract

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T cells, in which protein kinase C-6 (PKC-O) localizes to the contact point between T cells and antigen- presenting cells, in human and mouse Tregs, PKC-6 localizes to the opposite end of the cell in the distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified the intermediate filament vimentin as a PKC-6 phospho target and show that vimentin forms a DPC superstructure on which PKC-6 accumulates. Treatment of mouse Tregs with either a clinically relevant PKC-6 inhibitor or vimentin siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity. Moreover, vimentin-disrupted mouse Tregs were significantly better than controls at suppressing alloreactive T cell priming in graft-versus-host disease (GVHD) and GVHD lethality, using a complete MHC-mismatch mouse model of acute GVHD (C57BL/6 donor into BALB/c host). Interestingly, vimentin disruption augmented the suppressor function of PKC-[theta]-deficient mouse Tregs. This suggests that enhanced Treg activity after PKC-6 inhibition is secondary to effects on vimentin, not just PKC-6 kinase activity inhibition. Our data demonstrate that vimentin is a key metabolic and functional controller of Treg activity and provide proof of principle that disruption of vimentin is a feasible, translationally relevant method to enhance Treg potency., Introduction Regulatory T cells (Tregs) are critical for maintaining immune homeostasis and preventing autoimmune and inflammatory disorders (1, 2). However, they also support cancer progression by suppressing antitumor immunity (3). [...]

Published
2018
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16. P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy

Author

Wanhainen, Kelsey M., primary, Peng, Changwei, additional, Zhou, Maggie H., additional, Macedo, Bruna de Gois, additional, O'Flanagan, Stephen, additional, Yang, Tingyuan, additional, Kelekar, Ameeta, additional, Burbach, Brandon J., additional, Borges da Silva, Henrique, additional, and Jameson, Stephen C., additional

Published
2022
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22. Autophagy

Author

KELEKAR, AMEETA

Published
2005

25. In Vitro Induction of Human Regulatory T-Cells (iTregs) Using Conditions of Low Tryptophan Plus Kynurenines

Author

Hippen, Keli L., primary, MacMillan, Margaret L., additional, Lemire, Amanda, additional, Saha, Asim, additional, Hanse, Eric, additional, Lord, Colin, additional, Kelekar, Ameeta, additional, O'Connor, Roddy S., additional, Riley, James L., additional, June, Carl H, additional, Kean, Leslie, additional, Miller, Jeffrey S., additional, Wagner, John E., additional, Munn, David H., additional, and Blazar, Bruce R., additional

Published
2016
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27. Abstract 44: Hexyl-benzyl-biguanide (HBB) potently and selectively inhibits CYP3A4 epoxygenase activity and inhibits EET stabilization of mitochondrial respiration in ER+HER2- breast cancer cells, inducing glycolysis and pyruvate biosynthesis

Author

Guo, Zhijun, primary, Sevrioukova, Irina, additional, Hanse, Eric, additional, Zhang, Xia, additional, Denisov, Ilia, additional, Chiu, Ting-Lan, additional, Cuellar, Rebecca, additional, Torres, Christian, additional, Wulfkuhle, Julia, additional, Petricoin, Emanuel, additional, Cao, Qing, additional, Chu, Haitao, additional, Norris, Beverly, additional, Schumacher, Robert, additional, Kelekar, Ameeta, additional, Blair, Ian, additional, Capdevila, Jorge, additional, Falck, John, additional, Poulos, Thomas, additional, Sligar, Steven, additional, Georg, Gunda, additional, Amin, Elizabeth, additional, and Potter, David A., additional

Published
2016
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28. Protein Kinase C-θ and vimentin modulate multiple facets of Regulatory T-cell function.

Author

McDonald-Hyman, Cameron, primary, Thangavelu, Govindarajan, additional, Saha, Asim, additional, Muller, James, additional, Zhang, Guoan, additional, Kumari, Sudha, additional, Koehn, Brent H., additional, Mitchell, Jason S., additional, Fife, Brian T, additional, Serody, Jonathan S, additional, Osborn, Mark J, additional, Hippen, Keli L, additional, Kelekar, Ameeta, additional, Munn, David H, additional, Altman, Amnon, additional, Neubert, Thomas, additional, Dustin, Michael L, additional, and Blazar, Bruce R, additional

Published
2016
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29. Protein Kinase C-Theta Interacts with mTORC2 and Vimentin to Limit Regulatory T-Cell Function

Author

McDonald-Hyman, Cameron, primary, Thangavelu, Govindarajan, additional, Muller, James, additional, Zhang, Guoan, additional, Kumari, Sudha, additional, Saha, Asim, additional, Koehn, Brent H., additional, Mitchell, Jason S., additional, Fife, Brian T, additional, Serody, Jonathan S., additional, Osborn, Mark J., additional, Hippen, Keli L., additional, Kelekar, Ameeta, additional, Munn, David H., additional, Altman, Amnon, additional, Neubert, Thomas A., additional, Dustin, Michael L., additional, and Blazar, Bruce R., additional

Published
2015
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36. 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, Askew, David S., Baba, Misuzu, Baehrecke, Eric H., Bahr, Ben A., Ballabio, Andrea, Bamber, Bruce A., Bassham, Diane C., Bergamini, Ettore, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S., Breclesen, Dale E., Brodsky, Jeffrey, Brumell, John H., Brunk, Ulf T., Bursch, Wilfried, Camougrand, Nadine, Cebollero, Eduardo, Cecconi, Francesco, Chen, Yingyu, Chin, Lih-Shen, Choi, Augustine, Chu, Charleen T., Chung, Jongkyeong, Clarke, Peter G. H., Clark, Robert S. B., Clarke, Steven G., Clavé, Corinne, Cleveland, John L., Codogno, Patrice, Colombo, Maria I., Coto-Montes, Ana, Cregg, James M., Cuervo, Ana Maria, Debnath, Jayanta, Demarchi, Francesca, Dennis, Patrick B., Dennis, Phillip A., Deretic, Vojo, Devenish, Rodney J., Di Sano, Federica, Dice, J. Fred, Difiglia, Marian, Dinesh-Kumar, Savithramma, Distelhorst, Clark W., Djavaheri-Mergny, Mojgan, Dorsey, Frank C., Dröge, Wulf, Dron, Michel, Dunn Jr., William A., Duszenko, Michael, Eissa, N. Tony, Elazar, Zvulun, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Fesus, Laszlo, Finley, Kim D., Fuentes, José M., Fueyo, Juan, Fujisaki, Kozo, Galliot, Brigitte, Gao, Fen-Biao, Gewirtz, David A., Gibson, Spencer B., Gohla, Antje, Goldberg, Alfred L., Gonzalez, Ramon, González-Estévez, Cristina, Gorski, Sharon, Gottlieb, Roberta A., Häussinger, Dieter, He, You-Wen, Heidenreich, Kim, Hill, Joseph A., Hoyer-Hansen, Maria, Hu, Xun, Huang, Wei-Pang, Iwasaki, Akiko, Jäättelä, Marja, Jackson, William T., Jiang, Xuejun, Jin, Shengkan, Johansen, Terje, Jung, Jae U., Kadowaki, Motoni, Kang, Chanhee, Kelekar, Ameeta, Kessel, David H., Kiel, Jan A.K.W., Kim, Hong Pyo, Kimchi, Adi, Kinsella, Timothy J., Kiselyov, Kirill, Kitamoto, Katsuhiko, Knecht, Erwin, Komatsu, Masaaki, Kominami, Eiki, Konclo, Seiji, University of Michigan [Ann Arbor], University of Michigan System, Hebrew University of Jerusalem, Université Catholique de Louvain = Catholic University of Louvain (UCL), Creighton University, The University of Texas Health Science Center at Houston (UTHealth), University of Cincinnati (UC), Department of Chemical and Biological Sciences, University of Huddersfield, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), University of Connecticut (UCONN), Telethon Institute of Genetics and Medicine, University of Toledo, Department of Genetics, Development, and Cell Biology, Iowa State University (ISU), Universita degli studi di Pisa, Basic Medical Sciences, Western University of Health Sciences, Centre National de la Recherche Scientifique (CNRS), Indiana University, Indiana University System, Buck Institute for Research on Aging, Department of Biological Sciences, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Massachusetts General Hospital [Boston], Cell Biology Program, Utrecht University [Utrecht], Linköping University (LIU), Medizinische Universität Wien = Medical University of Vienna, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Università degli Studi di Roma Tor Vergata [Roma], Peking University, School of Medicine / Department of Pharmacology, University of California, Harvard University [Cambridge], Pennsylvania Commonwealth System of Higher Education (PCSHE), Korea Advanced Institute of Science and Technology (KAIST), Université de Lausanne (UNIL), Department of Chemistry and Biochemistry, University of California [Los Angeles] (UCLA), University of California-University of California, Molecular Biology Institute, Université de Bordeaux Ségalen [Bordeaux 2], Scripps Research Institute, Université Paris-Sud - Paris 11 (UP11), Signalisation et physiopathologie des cellules épithéliales, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Oviedo [Oviedo], Keck Graduate Institute [Claremont, Californie] (KGI), Albert Einstein College of Medicine [New York], University of California [San Francisco] (UCSF), Consorzio Interuniversitario, National Cancer Institute, The University of New Mexico [Albuquerque], Monash University, Dipartimento Biol, University of Naples Federico II, Tufts University, Dept Neurol, Syngenta, Yale University, Partenaires INRAE, Case Western Reserve University [Cleveland], University Hospitals of Cleveland, Immunotec Research Ltd., Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), University of Florida [Gainesville] (UF), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Baylor College of Medicine (BCM), Department of Biological Chemistry, Weizmann Institute of Science [Rehovot, Israël], University of Helsinki, University of Debrecen, Hungarian Academy of Sciences (MTA), Salk Institute for Biological Studies, Plant Molecular and Cellular Biology Laboratory, Universidad de Extremadura (UEX), University of Texas, Kagoshima University, Department of Zoology and Animal Biology, University of Geneva [Switzerland], Virginia Commonwealth University (VCU), University of Manitoba, University of Manitoba [Winnipeg], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Cell Biology, Charles University [Prague] (CU), University of Nottingham, UK (UON), British Columbia Cancer Agency, San Diego State University (SDSU), Duke University [Durham], University of Colorado [Boulder], University of Texas Southwestern Medical Center, Danish Cancer Society, Zhejiang University, National Taiwan Normal University (NTNU), Yale University [New Haven], Medical College of Wisconsin, Memorial Sloan Kettering Cancer Center, The University of Texas M.D. Anderson Cancer Center [Houston], University of Medecine and Dentistry of New Jersey, and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], phagophore, stress, [SDV]Life Sciences [q-bio], autophagosome, autolysosome
Abstract

La liste complète des auteurs est disponible sur la notice WOS : http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=INRA&SrcApp=INRA&DestLinkType=FullRecord&DestApp=WOS&KeyUT=ISI:000253008800003; International audience

Published
2008

39. The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8+T cells

Author

Borges da Silva, Henrique, Beura, Lalit K., Wang, Haiguang, Hanse, Eric A., Gore, Reshma, Scott, Milcah C., Walsh, Daniel A., Block, Katharine E., Fonseca, Raissa, Yan, Yan, Hippen, Keli L., Blazar, Bruce R., Masopust, David, Kelekar, Ameeta, Vulchanova, Lucy, Hogquist, Kristin A., and Jameson, Stephen C.

Abstract

Extracellular ATP (eATP) is an ancient ‘danger signal’ used by eukaryotes to detect cellular damage1. In mice and humans, the release of eATP during inflammation or injury stimulates both innate immune activation and chronic pain through the purinergic receptor P2RX72–4. It is unclear, however, whether this pathway influences the generation of immunological memory, a hallmark of the adaptive immune system that constitutes the basis of vaccines and protective immunity against re-infection5,6. Here we show that P2RX7 is required for the establishment, maintenance and functionality of long-lived central and tissue-resident memory CD8+T cell populations in mice. By contrast, P2RX7 is not required for the generation of short-lived effector CD8+T cells. Mechanistically, P2RX7 promotes mitochondrial homeostasis and metabolic function in differentiating memory CD8+T cells, at least in part by inducing AMP-activated protein kinase. Pharmacological inhibitors of P2RX7 provoked dysregulated metabolism and differentiation of activated mouse and human CD8+T cells in vitro, and transient P2RX7 blockade in vivo ameliorated neuropathic pain but also compromised production of CD8+memory T cells. These findings show that activation of P2RX7 by eATP provides a common currency that both alerts the nervous and immune system to tissue damage, and promotes the metabolic fitness and survival of the most durable and functionally relevant memory CD8+T cell populations.

Published
2018
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40. Guidelines for the use and interpretation of assays for monitoring autophagy.

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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. Y., Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S., Swanton, Charles, Sweeney, Sean T., Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takacs-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, 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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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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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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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. 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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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41. 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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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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43. 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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