The Open State Selectivity of the Bean Seed VDAC Depends on Stigmasterol and Ion Concentration.

The voltage-dependent anion channel (VDAC) is the major pathway for metabolites and ions transport through the mitochondrial outer membrane. It can regulate the flow of solutes by switching to a low conductance state correlated with a selectivity reversal, or by a selectivity inversion of its open state. The later one was observed in non-plant VDACs and is poorly characterized. We aim at investigating the selectivity inversion of the open state using plant VDAC purified from Phaseolus coccineus (PcVDAC) to evaluate its physiological role. Our main findings are: (1) The VDAC selectivity inversion of the open state occurs in PcVDAC, (2) Ion concentration and stigmasterol affect the occurrence of the open state selectivity inversion and stigmasterol appears to interact directly with PcVDAC. Interestingly, electrophysiological data concerning the selectivity inversion of the PcVDAC open state suggests that the phenomenon probably does not have a significant physiological effect in vivo.

Origin of ion selectivity in Phaseolus coccineus mitochondrial VDAC.

The mitochondrial voltage-dependent a nion-selective channel (VDAC) is the major permeation pathway for small ions and metabolites. Although a wealth of electrophysiological data has been obtained on different VDAC species, the physical mechanisms of their ionic selectivity are still elusive. We addressed this issue using electrophysiological experiments performed on plant VDAC. A simple macroscopic electrodiffusion model accounting for ion diffusion and for an effective fixed charge of the channel describes well its selectivity. Brownian Dynamics simulations of ion permeation performed on plant and mammalian VDACs point to the role of specific charged residues located at about the middle of the pore.