Phospholipids Regulate the Voltage-Dependence and Selectivity of Plant VDAC

Abstract

Membrane lipids have a significant effect on both structure and function of membrane proteins. Several comprehensive studies on the lipid composition of cell membranes indicate a high degree of adaptability to both endogenous and environmental cues. It is of physiological importance notably for plants which are static organisms to avoid lethal membrane injuries. VDAC channel constitutes the major transmembrane protein of the mitochondrial outer membrane, and is a key element in the regulation of solute exchange between mitochondria and cytoplasm. We have recently shown that sterol-VDAC interactions significantly affect the VDAC properties [1]. The present study further explores these lipid-protein interactions with special emphasis on the effect of phospholipid headgroups. The VDAC was reconstituted in planar lipid bilayer formed from either DOPC or DOPE or a DOPE/DOPC mixture. The main findings of this study are: (a) DOPE is essential for the channel gating at salt concentration prevailing in vivo and the voltage-dependence is inhibited when DOPE is replaced by DOPC (b) in the presence of a DOPC/DOPE mixture, the DOPE molal fraction require to restore the VDAC gating is lower than that required to change the membrane viscosity, c) the unitary conductance is not affected by the DOPC or DOPE, (d) both selectivity and voltage-dependence are modulated by the degree of methylation of the DOPE but not the single channel conductance and the gating parameters. The high resolution structure of mammalian VDAC was used as a template to identify putative residues able to interact with PE headgroups. All together these results indicate that there is a direct interaction between PE and the VDAC and that PC locks the VDAC in its open state inhibiting transitions of the VDAC to the subconductance states. [1] Mlayeh et al. Biophys.J. (2010),doi:10.1016/j.bpj.2010.07.067