Toxic proteins released from mitochondria in cell death

被引:686
作者
Saelens, X
Festjens, N
Vande Walle, L
van Gurp, M
van Loo, G
Vandenabeele, P
机构
[1] VIB, Dept Mol & Biomed Res, Mol Signalling & Cell Death Unit, B-9052 Ghent, Belgium
[2] State Univ Ghent, B-9052 Ghent, Belgium
[3] EMBL Monterotondo, Mouse Biol Program, I-00016 Monterotondo, Italy
关键词
mitochondria; cytochrome c; Smac/DIABLO; endonuclease G; AIF; HtrA2/OMI;
D O I
10.1038/sj.onc.1207523
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
A plethora of apoptotic stimuli converge on the mitochondria and affect their membrane integrity. As a consequence, multiple death-promoting factors residing in the mitochondrial intermembrane space are liberated in the cytosol. Pro- and antiapoptotic Bcl-2 family proteins control the release of these mitochondrial proteins by inducing or preventing permeabilization of the outer mitochondrial membrane. Once released into the cytosol, these mitochondrial proteins activate both caspase-dependent and -independent cell death pathways. Cytochrome c was the first protein shown to be released from the mitochondria into the cytosol, where it induces apoptosome formation. Other released mitochondrial proteins include apoptosis-inducing factor (AIF) and endonuclease G, both of which contribute to apoptotic nuclear DNA damage in a caspase-independent way. Other examples are Smac/DIABLO(second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI) and the serine protease HtrA2/OMI (high-temperature requirement protein A2), which both promote caspase activation and instigate caspase-independent cytotoxicity. The precise mode of action and importance of cytochrome c in apoptosis in mammalian cells has become clear through biochemical, structural and genetic studies. More recently identified factors, for example HtrA2/OMI and Smac/DIABLO, are still being studied intensively in order to delineate their functions in apoptosis. A better understanding of these functions may help to develop new strategies to treat cancer.
引用
收藏
页码:2861 / 2874
页数:14
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