On the role of VDAC in apoptosis: fact and fiction.
Research on VDAC has accelerated as evidence grows of its importance in mitochondrial function and in apoptosis. New investigators entering the field are often confounded by the VDAC literature and its many apparent conflicts and contradictions. This review is an effort to shed light on the situation and identify reliable information from more questionable claims. Our views on the most important controversial issues are as follows: VDAC is only present in the mitochondrial outer membrane. VDAC functions as a monomer. VDAC functions normally with or without Ca(2+). It does not form channels that mediate the flux of proteins through membranes (peptides and unfolded proteins are excluded from this statement). Closure of VDAC, not VDAC opening, leads to mitochondria outer membrane permeabilization and apoptosis.
Rostovtseva
Tatiana K
TK
Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. rostovtt@mail.nih.gov
Tan
Wenzhi
W
Colombini
Marco
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D019281:Dimerization; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000502:physiology*
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050994:Voltage-Dependent Anion Channels; D006593:Hexokinase; D002118:Calcium