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In the mitochondrial pathway of apoptosis, caspase activationis closely linked to mitochondrial outer membrane permeabilization(MOMP). Numerous pro-apoptotic signal-transducing moleculesand pathological stimuli converge on mitochondria to induceMOMP. The local regulation and execution of MOMP involve proteinsfrom the Bcl-2 family, mitochondrial lipids, proteins that regulatebioenergetic metabolite flux, and putative components of thepermeability transition pore. MOMP is lethal because it resultsin the release of caspase-activating molecules and caspase-independentdeath effectors, metabolic failure in the mitochondria, or both.Drugs designed to suppress excessive MOMP may avoid pathologicalcell death, and the therapeutic induction of MOMP may restoreapoptosis in cancer cells in which it is disabled. The generalrules governing the pathophysiology of MOMP and controversialissues regarding its regulation are discussed.
1 Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA. 2 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
* To whom correspondence should be addressed. E-mail: doug{at}liai.org (D.R.G.) and kroemer{at}igr.fr (G.K.)
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Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins.
C. Brooks, Q. Wei, L. Feng, G. Dong, Y. Tao, L. Mei, Z.-J. Xie, and Z. Dong (2007)
PNAS
104, 11649-11654
|Abstract »|Full Text »|PDF »
A Novel Epidermal Growth Factor Receptor Inhibitor Promotes Apoptosis in Non-Small Cell Lung Cancer Cells Resistant to Erlotinib.
T. de La Motte Rouge, L. Galluzzi, K. A. Olaussen, Y. Zermati, E. Tasdemir, T. Robert, H. Ripoche, V. Lazar, P. Dessen, F. Harper, et al. (2007)
Cancer Res.
67, 6253-6262
|Abstract »|Full Text »|PDF »
A Novel Bcl-2-Like Inhibitor of Apoptosis Is Encoded by the Parapoxvirus Orf Virus.
D. Westphal, E. C. Ledgerwood, M. H. Hibma, S. B. Fleming, E. M. Whelan, and A. A. Mercer (2007)
J. Virol.
81, 7178-7188
|Abstract »|Full Text »|PDF »
Chemopreventive effects of lupulone, a hop {beta}-acid, on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis.
V. Lamy, S. Roussi, M. Chaabi, F. Gosse, N. Schall, A. Lobstein, and F. Raul (2007)
Carcinogenesis
28, 1575-1581
|Abstract »|Full Text »|PDF »
