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 Ca2+ flux across the outer membrane occurs mainly through VDAC. Since both Ca2+ fluxes and VDAC are involved in apoptosis, we examined whether Ca2+ is required for channel formation by VDAC isolated from rat liver. The voltage gating of VDAC does not require Ca2+ and it functions normally with or without Ca2+. Additionally, VDAC generally shows a higher permeability to Ca2+ in the closed states (states with lower permeability to metabolites) than that in the open state. Thus VDAC closure, which induces apoptosis, also favors Ca2+ 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. (C) 2007 Elsevier B.V. All rights reserved.