Molecular Origin of Ion Selectivity in Phaseolus Coccineus Mitochondrial VDAC

Abstract

The mitochondrial voltage-dependent anion-selective channel (VDAC) is the major permeation pathway for small ions and metabolites through the mitochondrial outer membrane. The deciphering of the mechanism underpinning anion transport through the VDAC and of its selectivity is important as most of the chemical species entering or leaving the mitochondrion are anions that are directly involved in respiration. 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.Here we examined the ionic selectivity of the open state of the plant PcVDAC experimentally and theoretically. We demonstrated that a simple one-compartment macroscopic electrodiffusion model including both ion diffusion and an effective fixed charge in the pore can properly describe the selectivity of the channel. Using Brownian Dynamics (BD) simulations performed on plant and mammalian VDACs we also proposed a comprehensive detailed model of the molecular mechanism of ion permeation.