VDAC closure increases calcium ion flux.
VDAC is the major permeability pathway in the mitochondrial outer membrane and can control the flow of metabolites and ions. Therefore Ca(2+) flux across the outer membrane occurs mainly through VDAC. Since both Ca(2+) fluxes and VDAC are involved in apoptosis, we examined whether Ca(2+) is required for channel formation by VDAC isolated from rat liver. The voltage gating of VDAC does not require Ca(2+) and it functions normally with or without Ca(2+). Additionally, VDAC generally shows a higher permeability to Ca(2+) in the closed states (states with lower permeability to metabolites) than that in the open state. Thus VDAC closure, which induces apoptosis, also favors Ca(2+) flux into mitochondria, which can also lead to permeability transition and cell death. These results are consistent with the view that VDAC closure is a pro-apoptotic signal.
Tan
Wenzhi
W
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Colombini
Marco
M
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D015640:Ion Channel Gating; D009994:Osmolar Concentration; D010539:Permeability; D051381:Rats; D050994:Voltage-Dependent Anion Channels / Q000502:physiology*
D002712:Chlorides; D050994:Voltage-Dependent Anion Channels; D002118:Calcium