The voltage-dependent anion channel: an essential player in apoptosis.
The increase of outer mitochondrial membrane permeability is a central event in apoptotic cell death, since it releases several apoptogenic factors such as cytochrome c into the cytoplasm that activate the downstream destructive processes. The voltage-dependent anion channel (VDAC or mitochondrial porin) plays an essential role in the increase of mitochondrial membrane permeability, and it is regulated by the Bcl-2 family of proteins via direct interaction. Anti-apoptotic Bcl-2 family members close the VDAC, whereas some (but not all) pro-apoptotic members interact with the VDAC to generate a protein-conducting channel through which cytochrome c can pass. Although the VDAC is directly involved in the apoptotic increase of mitochondrial membrane permeability and is known to be a component of the permeability transition pore complex, its role in the regulation of outer membrane permeability can be separated from the occurrence of permeability transition events, such as mitochondrial swelling followed by rupture of the outer mitochondrial membrane. The VDAC not only interacts with Bcl-2 family members, but also with other proteins, and probably acts as a convergence point for a variety of life-or-death signals.
Tsujimoto
Yoshihide
Y
Osaka University Medical School and Graduate School of Medicine, Laboratory of Molecular Genetics and CREST of Japanese Science & Technology, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. tsujimot@gene.med.osaka-u.ac.jp
Shimizu
Shigeomi
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018272:Porins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein
D003574:Cytochrome c Group; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018272:Porins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D002118:Calcium