The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet

被引:509
作者
van Loo, G
Saelens, X
van Gurp, M
MacFarlane, M
Martin, SJ
Vandenabeele, P
机构
[1] State Univ Ghent VIB, Mol Signalling & Cell Death Unit, Dept Mol Biomed Res, B-9000 Ghent, Belgium
[2] Univ Leicester, Med Res Council, Toxicol Unit, Leicester, Leics, England
[3] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Mol Cell Biol Lab, Dublin, Ireland
关键词
apoptosis; mitochondria; apoptosome; caspase;
D O I
10.1038/sj.cdd.4401088
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria are 'life-essential' organelles for the production of metabolic energy in the form of ATP. Paradoxically mitochondria also play a key role in controlling the pathways that lead to cell death. This latter role of mitochondria is more than just a 'loss of function' resulting in an energy deficit but is an active process involving different mitochondrial proteins. Cytochrome c was the first characterised mitochondrial factor shown to be released from the mitochondrial intermembrane space and to be actively implicated in apoptotic cell death. Since then, other mitochondrial proteins, such as AlF, Smac/DIABLO, endonuclease G and Omi/HtrA2, were found to undergo release during apoptosis and have been implicated in various aspects of the cell death process. Members of the Bcl-2 protein family control the integrity and response of mitochondria to apoptotic signals. The molecular mechanism by which mitochondrial intermembrane space proteins are released and the regulation of mitochondrial homeostasis by Bcl-2 proteins is still elusive. This review summarises and evaluates the current knowledge concerning the complex role of released mitochondrial proteins in the apoptotic process.
引用
收藏
页码:1031 / 1042
页数:12
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