VDAC regulation by the Bcl-2 family of proteins.
The Bcl-2 family of proteins consists of anti-apoptotic and pro-apoptotic members, which determine the life or death of cells by altering mitochondrial membrane permeability. Pro-apoptotic Bcl-2 family members increase mitochondrial membrane permeability, resulting in the release of mitochondrial apoptogenic factors such as cytochrome c that activates death proteases called caspases, whereas anti-apoptotic family members prevent this increase of mitochondrial membrane permeability. The release of cytochrome c is central to apoptotic signal transduction in mammals, and has been studied extensively, leading to the development of several models for cytochrome c release including rupture of the mitochondrial outer membrane and involvement of specific channels. This article describes the important role of a mitochondrial outer membrane channel, the voltage-dependent anion channel (VDAC), in apoptogenic cytochrome c release and its regulation by Bcl-2 family members, and also discusses the molecular architecture of the life - death switch in mammalian cells. Cell Death and Differentiation (2000) 7, 1174 - 1181
Tsujimoto
Y
Y
Department of Medical Genetics, Biomedical Research Center, Osaka University Graduate School of Medicine, CREST of Japan Science and Technology Corp. (JST), Suita, Osaka, Japan. tsujimot@gene.med.osaka-u.ac.jp
Shimizu
S
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D018272:Porins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050994:Voltage-Dependent Anion Channels
D003574:Cytochrome c Group; D018272:Porins; D019253:Proto-Oncogene Proteins c-bcl-2; D050994:Voltage-Dependent Anion Channels