14 results on '"Atan Gross"'
Search Results
2. PERPHERAL BLOOD CELL MITOCHONDRIAL DYSFUNCTION IN MYELODYSPLASTIC SYNDROMECAN BE IMPROVED BY A COMBINATION OF COENZYME Q10 AND CARNITINE
- Author
-
Kalman Filanovsky, Michal Haran, Vita Mirkin, Andrei Braester, Olga Shevetz, Anfisa Stanevsky, Erica Sigler, Ekaterina Votinov, Yehudit Zalzman-Amir, Alain Berrebi, Atan Gross, and Lev Shvidel
- Subjects
myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer. ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Structural mitochondrial abnormalities as well as genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS) , yet there is currently little data regarding the metabolic properties and energy production of MDS cells. In the current study we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls We then assessed the effect of food supplements- Coenzyme Q10 and carnitine on mitochondrial function and hematological response .We show here for the first time that in low risk MDS there is a significant impairment of mitochondrial respiration in peripheral blood cells and this can be improved with food supplements. We also show that such myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer. supplements lead to improvement in cytopenia's and quality of life.
- Published
- 2020
- Full Text
- View/download PDF
3. Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function
- Author
-
Flurin Item, Stephan Wueest, Vera Lemos, Sokrates Stein, Fabrizio C. Lucchini, Rémy Denzler, Muriel C. Fisser, Tenagne D. Challa, Eija Pirinen, Youngsoo Kim, Silvio Hemmi, Erich Gulbins, Atan Gross, Lorraine A. O’Reilly, Markus Stoffel, Johan Auwerx, and Daniel Konrad
- Subjects
Science - Abstract
Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.
- Published
- 2017
- Full Text
- View/download PDF
4. Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity
- Author
-
Liat Buzaglo-Azriel, Yael Kuperman, Michael Tsoory, Yehudit Zaltsman, Liat Shachnai, Smadar Levin Zaidman, Elad Bassat, Inbal Michailovici, Alona Sarver, Eldad Tzahor, Michal Haran, Cecile Vernochet, and Atan Gross
- Subjects
Biology (General) ,QH301-705.5 - Published
- 2017
- Full Text
- View/download PDF
5. Competitive Bone-marrow Transplantations
- Author
-
Maria Maryanovich and Atan Gross
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Competitive bone marrow transplantation assay measures multi-lineage reconstitution of hematopoiesis in irradiated transplant recipient mice. Thus this assay is routinely used to determine haematopoietic stem and progenitor cells (HSPCs) functionality in vivo. The principle of the method is to transplant bone marrow donor cells (derived from transgenic mice of choice) on C57BL6 background together with normal competitor bone marrow. In order to distinguish donor from competitor cells upon transplantation, usually competitor mice are congenic and carry the differential B cell antigen originally designated Ly5.1 and CD45.1.A typical competitive bone marrow transplantation experiment will contain two transplantation groups, donor (transgenic mice of choice and their controls) are transplanted in competition with normal competitors and engraftment efficiency is evaluated in both blood and bone marrow.
- Published
- 2014
- Full Text
- View/download PDF
6. MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells
- Author
-
Michael Mullokandov, Jacob H. Hanna, Dilshad H. Khan, Atan Gross, Emmanuel Amzallag, Yehudit Zaltsman, Amir Bahat, Vladislav Krupalnik, Coral Halperin, Ayelet Erez, Andres Goldman, Alon Silberman, and Aaron D. Schimmer
- Subjects
0301 basic medicine ,Dynamins ,Pluripotent Stem Cells ,Science ,Regulator ,General Physics and Astronomy ,Gene Expression ,Mitochondrion ,Mitochondrial Dynamics ,Mitochondrial Membrane Transport Proteins ,General Biochemistry, Genetics and Molecular Biology ,Article ,GTP Phosphohydrolases ,03 medical and health sciences ,Mice ,Gene expression ,Animals ,lcsh:Science ,Induced pluripotent stem cell ,Cells, Cultured ,Mice, Knockout ,Multidisciplinary ,Microscopy, Confocal ,biology ,Chemistry ,Mouse Embryonic Stem Cells ,General Chemistry ,Nanog Homeobox Protein ,Embryonic stem cell ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,Histone ,mitochondrial fusion ,Acetylation ,biology.protein ,lcsh:Q - Abstract
The role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization. In contrast, MTCH2−/− ESCs fail to elongate their mitochondria and to alter their metabolism, maintaining high levels of histone acetylation and expression of naïve pluripotency markers. Importantly, enforced mitochondria elongation by the pro-fusion protein Mitofusin (MFN) 2 or by a dominant negative form of the pro-fission protein dynamin-related protein (DRP) 1 is sufficient to drive the exit from naïve pluripotency of both MTCH2−/− and wild-type ESCs. Taken together, our data indicate that mitochondria elongation, governed by MTCH2, plays a critical role and constitutes an early driving force in the naïve-to-primed pluripotency interconversion of murine ESCs., Reprogramming of mitochondria metabolism occurs during naïve to primed pluripotency differentiation in mouse embryonic stem cells (ESCs). Here the authors show that mitochondrial MTCH2 regulates mitochondrial fusion and that this fusion is required for naïve to primed pluripotency conversion
- Published
- 2018
7. Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function
- Author
-
Fabrizio C. Lucchini, Johan Auwerx, Rémy Denzler, Tenagne D. Challa, Eija Pirinen, Daniel Konrad, Stephan Wueest, Atan Gross, Lorraine A. O'Reilly, Youngsoo Kim, Silvio Hemmi, Erich Gulbins, Sokrates Stein, Flurin Item, Muriel C. Fisser, Markus Stoffel, Vera Lemos, A.I. Virtanen -instituutti, University of Zurich, and Konrad, Daniel
- Subjects
0301 basic medicine ,Male ,Medizin ,General Physics and Astronomy ,Mice, Obese ,Mitochondria, Liver ,Mitochondrion ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Nonalcoholic fatty liver disease ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,Fatty liver ,Fatty Acids ,Type 2 diabetes ,Fas receptor ,Metabolic syndrome ,10124 Institute of Molecular Life Sciences ,3100 General Physics and Astronomy ,Liver ,030220 oncology & carcinogenesis ,medicine.medical_specialty ,Fas Ligand Protein ,Science ,10071 Functional Genomics Center Zurich ,1600 General Chemistry ,Mice, Transgenic ,Biology ,Diet, High-Fat ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Insulin resistance ,Lipid oxidation ,1300 General Biochemistry, Genetics and Molecular Biology ,Internal medicine ,medicine ,Animals ,fas Receptor ,Triglycerides ,General Chemistry ,medicine.disease ,Lipid Metabolism ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,10036 Medical Clinic ,570 Life sciences ,biology ,lcsh:Q ,Steatosis ,Insulin Resistance ,Non-alcoholic fatty liver disease - Abstract
Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance., published version, peerReviewed
- Published
- 2017
8. The Mitochondrial Transacylase, Tafazzin, Regulates AML Stemness by Modulating Intracellular Levels of Phospholipids
- Author
-
Mathieu Lupien, Yulia Jitkova, Michael Mullokandov, Helen Loo Yau, Rima Al-awar, James R. Hawley, Rose Hurren, Troy Ketela, S. Kim, Veronique Voisin, Neil MacLean, Daniel D. De Carvalho, Mark D. Minden, Geethu E. Thomas, Val A. Fajardo, Ahmed Aman, Zhenyue Hao, Zaza Khuchua, G. Wei Xu, Gary D. Bader, Richard P. Bazinet, Juan J. Aristizabal Henao, Mingjing Xu, Paul J. LeBlanc, Ayesh K. Seneviratne, Steven M. Claypool, Steven M. Chan, Xiaoming Wang, Atan Gross, Aaron D. Schimmer, Ken D. Stark, David Sharon, Raphaël Chouinard-Watkins, Danny V. Jeyaraju, Caitlin Schafer, and Marcela Gronda
- Subjects
Male ,Cell ,Tafazzin ,Mice, Transgenic ,Mice, SCID ,Mitochondrion ,Biology ,Article ,Mice ,chemistry.chemical_compound ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Cell Line, Tumor ,hemic and lymphatic diseases ,Cardiolipin ,Genetics ,medicine ,Animals ,Humans ,Receptor ,Phospholipids ,030304 developmental biology ,Gene knockdown ,0303 health sciences ,Toll-Like Receptors ,Myeloid leukemia ,Phosphatidylserine ,Cell Biology ,Mitochondria ,Cell biology ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,chemistry ,Doxorubicin ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Female ,Stem cell ,Acyltransferases ,030217 neurology & neurosurgery ,Intracellular ,Signal Transduction ,Transcription Factors - Abstract
Summary Tafazzin (TAZ) is a mitochondrial transacylase that remodels the mitochondrial cardiolipin into its mature form. Through a CRISPR screen, we identified TAZ as necessary for the growth and viability of acute myeloid leukemia (AML) cells. Genetic inhibition of TAZ reduced stemness and increased differentiation of AML cells both in vitro and in vivo. In contrast, knockdown of TAZ did not impair normal hematopoiesis under basal conditions. Mechanistically, inhibition of TAZ decreased levels of cardiolipin but also altered global levels of intracellular phospholipids, including phosphatidylserine, which controlled AML stemness and differentiation by modulating toll-like receptor (TLR) signaling.
- Published
- 2019
9. Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity
- Author
-
Atan Gross, Yehudit Zaltsman, Michael Tsoory, Smadar Levin Zaidman, Eldad Tzahor, Yael Kuperman, Elad Bassat, Liat Buzaglo-Azriel, Michal Haran, Cecile Vernochet, Liat Shachnai, Inbal Michailovici, and Alona Sarver
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Gene Expression ,030209 endocrinology & metabolism ,Oxidative phosphorylation ,Mitochondrion ,Biology ,Diet, High-Fat ,Mitochondrial Membrane Transport Proteins ,Oxidative Phosphorylation ,General Biochemistry, Genetics and Molecular Biology ,Energy homeostasis ,Mice ,03 medical and health sciences ,Mitochondrial membrane transport protein ,0302 clinical medicine ,Endurance training ,Physical Conditioning, Animal ,Internal medicine ,medicine ,Hyperinsulinemia ,Animals ,Humans ,Glycolysis ,Obesity ,Muscle, Skeletal ,Mitochondrial Carrier Homolog 2 ,lcsh:QH301-705.5 ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,medicine.disease ,Mitochondria ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Body Composition ,Metabolome ,biology.protein ,Energy Metabolism - Abstract
SummaryMitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis.
- Published
- 2017
10. The distribution and apoptotic function of outer membrane proteins depend on mitochondrial fusion
- Author
-
Atan Gross, Péter Várnai, David Weaver, György Hajnóczky, Verónica Eisner, László Hunyady, and Xingguo Liu
- Subjects
Muscle Fibers, Skeletal ,MFN2 ,Mitochondrion ,Biology ,Mitochondrial apoptosis-induced channel ,Mitochondrial Dynamics ,Article ,Cell Line ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Gene Knockout Techniques ,Mice ,MFN1 ,Inner membrane ,Animals ,Humans ,Molecular Biology ,Voltage-Dependent Anion Channel 2 ,Cell Biology ,Mitochondrial carrier ,Cell biology ,Rats ,Protein Transport ,bcl-2 Homologous Antagonist-Killer Protein ,mitochondrial fusion ,Mitochondrial Membranes ,biological phenomena, cell phenomena, and immunity ,Bcl-2 Homologous Antagonist-Killer Protein ,BH3 Interacting Domain Death Agonist Protein - Abstract
Cells deficient in mitochondrial fusion have been shown to have defects linked to the exchange of inner membrane and matrix components. Because outer-mitochondrial membrane (OMM) constituents insert directly from the cytoplasm, a role for fusion in their intermitochondrial transfer was unanticipated. Here, we show that fibroblasts lacking the GTPases responsible for OMM fusion, mitofusins 1 and 2 (MFN1 and MFN2), display more heterogeneous distribution of OMM proteins. Proteins with different modes of OMM association display varying degrees of heterogeneity in Mfn1/2(-/-) cells and different kinetics of transfer during fusion in fusion-competent cells. Proapoptotic Bak exhibits marked heterogeneity, which is normalized upon expression of MFN2. Bak is critical for Bid-induced OMM permeabilization and cytochrome c release, and Mfn1/2(-/-) cells show dysregulation of Bid-dependent apoptotic signaling. Bid sensitivity of Bak-deficient mitochondria is regained upon fusion with Bak-containing mitochondria. Thus, OMM protein distribution depends on mitochondrial fusion and is a locus of apoptotic dysfunction in conditions of fusion deficiency.
- Published
- 2014
11. BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts
- Author
-
Tak W. Mak, Rachel Sarig, Richard A. Flavell, Atan Gross, Richard C. Marcellus, and Yehudit Zaltsman
- Subjects
Apoptosis ,Cytochrome c Group ,Caspase 3 ,Simian virus 40 ,Bioinformatics ,Caspase 8 ,Biochemistry ,Mice ,Western blot ,medicine ,Animals ,APAF1 ,Molecular Biology ,Cells, Cultured ,Caspase-9 ,medicine.diagnostic_test ,biology ,Chemistry ,Cytochrome c ,Wild type ,Proteins ,Cell Biology ,Caspase 9 ,Mitochondria ,Cell biology ,Apoptotic Protease-Activating Factor 1 ,Caspases ,Mutation ,biology.protein ,Additions and Corrections ,Carrier Proteins ,BH3 Interacting Domain Death Agonist Protein - Abstract
The proapoptotic activity of BID seems to solely depend upon its cleavage to truncated tBID. Here we demonstrate that expression of a caspase-8 non-cleavable (nc) BID-D59A mutant or expression of wild type (wt) BID induces apoptosis in Bid -/-, caspase-8 -/-, and wt primary MEFs. Western blot analysis indicated that no cleavage products appeared in cells expressing ncBID. ncBID was as effective as wtBID in inducing cytochrome c release, caspase activation, and apoptosis. ncBID and wtBID (nc/wtBID) were much less effective than tBID in localizing to mitochondria and in inducing cytochrome c release, but only slightly less effective in inducing apoptosis. Studies with Apaf-1- and caspase-9-deficient primary MEFs indicated that both proteins were essential for nc/wtBID and for tBID-induced apoptosis. Most importantly, expression of non-apoptotic levels of either ncBID or wtBID in Bid -/- MEFs induced a similar and significant enhancement in apoptosis in response to a variety of death signals, which was accompanied by enhanced localization of BID to mitochondria and cytochrome c release. Thus, these results implicate full-length BID as an active player in the mitochondria during apoptosis.
- Published
- 2012
12. Utilizing mitochondrial events as biomarkers for imaging apoptosis
- Author
-
Yoseph Addadi, M Eifer, Atan Gross, N Yivgi-Ohana, and Michal Neeman
- Subjects
Yellow fluorescent protein ,Cancer Research ,Time Factors ,Immunology ,Mice, Nude ,Apoptosis ,macromolecular substances ,Mitochondrion ,Mitochondrial apoptosis-induced channel ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Bimolecular fluorescence complementation ,0302 clinical medicine ,Bcl-2-associated X protein ,Bacterial Proteins ,intravital microscopy ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,protein interaction ,programmed cell death ,Caspase ,bcl-2-Associated X Protein ,030304 developmental biology ,0303 health sciences ,biology ,Cytochrome c ,fungi ,Cytochromes c ,Cell Biology ,molecular imaging ,Molecular biology ,High-Throughput Screening Assays ,Mitochondria ,Rats ,Cell biology ,Luminescent Proteins ,Microscopy, Fluorescence ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Original Article - Abstract
Cells undergoing apoptosis show a plethora of time-dependent changes. The available tools for imaging apoptosis in live cells rely either on the detection of the activity of caspases, or on the visualization of exposure of phosphatidyl serine in the outer leaflet of the cell membrane. We report here a novel method for the detection of mitochondrial events during apoptosis, namely translocation of Bax to mitochondria and release of cytochrome c (Cyt c) using bimolecular fluorescence complementation. Expression of split yellow fluorescent protein (YFP) fragments fused to Bax and Cyt c, resulted in robust induction of YFP fluorescence at the mitochondria of apoptotic cells with very low background. In vivo expression of split YFP protein fragments in liver hepatocytes and intra-vital imaging of subcutaneous tumor showed elevated YFP fluorescence upon apoptosis induction. Thus, YFP complementation could be applied for high-throughput screening and in vivo molecular imaging of mitochondrial events during apoptosis.
- Published
- 2011
- Full Text
- View/download PDF
13. Mutagenesis of the BH3 Domain of BAX Identifies Residues Critical for Dimerization and Killing
- Author
-
Kun Wang, Stanley J. Korsmeyer, Atan Gross, and Gabriel Waksman
- Subjects
Programmed cell death ,Mutant ,Saccharomyces cerevisiae ,Molecular Sequence Data ,Repressor ,Apoptosis ,Cell Line ,Bcl-2-associated X protein ,Proto-Oncogene Proteins ,Animals ,Humans ,Amino Acid Sequence ,Binding site ,Molecular Biology ,Peptide sequence ,Cell Growth and Development ,Cell Line, Transformed ,bcl-2-Associated X Protein ,Binding Sites ,biology ,Bcl-2 family ,Cell Biology ,Intracellular Membranes ,biology.organism_classification ,Molecular biology ,Precipitin Tests ,Cell biology ,Mitochondria ,Rats ,Cross-Linking Reagents ,Proto-Oncogene Proteins c-bcl-2 ,biology.protein ,Mutagenesis, Site-Directed ,biological phenomena, cell phenomena, and immunity ,Dimerization - Abstract
Programmed cell death and its morphologic equivalent, apoptosis, are orchestrated by a distinct genetic pathway that is apparently possessed by all multicellular organisms (22). Moreover, the biochemical details of how encoded proteins function are beginning to emerge. The BCL-2 family of proteins constitutes a central decisional point within the common portion of the apoptotic pathway. This family possesses both proapoptotic (BAX, BAK, BCL-XS, BAD, BIK, BID, HRK, and BIM) and antiapoptotic (BCL-2, BCL-XL, MCL-1, and A1) molecules (5, 11). The ratio of antiapoptotic to proapoptotic molecules such as BCL-2/BAX determines the response to a proximal apoptotic signal (14). A striking characteristic of many family members is their propensity to form homo- and heterodimers (16, 19). The BCL-2 family has homology clustered principally within four conserved domains called BH1, BH2, BH3, and BH4 (5, 11). The multidimensional nuclear magnetic resonance (NMR) and X-ray crystallographic structure of a BCL-XL monomer indicates that the BH1-4 domains correspond to α helices 1 to 7. Notably, the BH1, -2, and -3 domains are in close proximity and create a hydrophobic pocket presumably involved in interactions with other BCL-2 family members (13). The NMR analysis of a BCL-XL-BAK BH3 peptide complex revealed both hydrophobic and electrostatic interactions between the BCL-XL pocket and a BH3 amphipathic α-helical peptide from BAK (17). Prior mutagenesis studies of BCL-2 and BCL-XL revealed the importance of BH1 and BH2 domains for both their antiapoptotic function and the capacity to heterodimerize with proapoptotic molecules like BAX or BAK (2, 19, 26). In general, most mutations that disrupt heterodimerization with BAX also lose their death repressor function. However, exceptions do exist; some mutants of BCL-XL fail to bind BAX or BAK but still repress cell death, suggesting that these functions can be separated for antiapoptotic molecules (2). Moreover, a genetic approach with Bcl-2-deficient and Bax-deficient mice also suggested that BCL-2 and BAX could function independently of one another (10). Deletion studies of the death agonist BAK first implicated the BH3 domain as having the capacity to bind BCL-XL and promote apoptosis (3). However, the functional significance of BH3 in BAX is uncertain as indicated in the literature. Three deletion analyses indicated the necessity of the BH3 domain in BAX to promote cell death as well as to heterodimerize with BCL-2 (3, 9, 28). Yet, two recent studies reported that BAX functions as a death activator independent of its heterodimerization (21, 27). Moreover, substitution mutants within the BH3 domain showed conflicting specificities of heterodimerization (20, 21, 27). Our initial screen of yeast two-hybrid libraries with BCL-2 as bait yielded multiple clones that possess only the NH2 terminus of BAX, bearing the BH3 but not the BH1 or the BH2 domains. A similar set of isolates was obtained when BCL-2 (G145A) was used as bait (15). We also noted by deletion analysis and assessment of minimal domains of BAX that the BH3 domain was required for both homodimerization and heterodimerization. Consequently, we undertook an extensive site-directed mutagenesis of the BH3 domain of BAX. These studies demonstrate the importance of the hydrophobic face of the amphipathic α helix of BH3 for the dimerization and cell death activities of BAX. Furthermore, analysis of a BAX mutant indicates that its retained conformation as a cross-linkable dimer at mitochondrial membranes correlates with its intact apoptotic function.
- Published
- 1998
14. Mitochondrial Carrier Homolog 2: A Clue to Cracking the BCL-2 Family Riddle?
- Author
-
Atan Gross
- Abstract
Abstract BCL-2 family members are pivotal regulators of the apoptotic process. Mitochondria are a major site-of-action for these proteins. Several prominent alterations occur to mitochondria during apoptosis that seem to be part of the “mitochondrial apoptotic program.” The BCL-2 family members are believed to be the major regulators of this program, however their exact mechanism of action still remains a mystery. BID, a pro-apoptotic BCL-2 family member plays an essential role in initiating this program. Recently, we have revealed that in apoptotic cells the activated/truncated form of BID, tBID, interacts with a novel, uncharacterized protein named mitochondrial carrier homolog 2 (Mtch2). Mtch2 is a conserved protein that is similar to members of the mitochondrial carrier protein (MCP) family. This review summarizes the current knowledge regarding BCL-2 family members and the mitochondrial apoptotic program and examines the possible involvement of Mtch2 in this program. [ABSTRACT FROM AUTHOR]
- Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.