The mitochondrial VDAC of bean seeds recruits phosphatidylethanolamine lipids for its proper functioning

The voltage-dependent anion-selective channel (VDAC) is the main pathway for inorganic ions and metabolites through the mitochondrial outer membrane. Studies recently demonstrated that membrane lipids regulate its function. It remains, however, unclear how this regulation takes place. In this study, we show that phospholipids are key regulators of Phaseolus VDAC function and, furthermore, that the salt concentration modulates this regulation. Both selectivity and voltage dependence of Phaseolus VDAC are very sensitive to a change in the lipid polar head from PC to PE. Interestingly enough, this dependence is observed only at low salt concentration. Furthermore, significant changes in VDAC functional properties also occur with the gradual methylation of the PE group pointing to the role of subtle chemical variations in the lipid head group. The dependence of PcVDAC gating upon the introduction of a small mole fraction of PE in a PC bilayer has prompted us to propose the existence of a specific interaction site for PE on the outer surface of PcVDAC. Eventually, comparative modeling and molecular dynamics simulations suggest a potential mechanism to get insight into the anion selectivity enhancement of PcVDAC observed in PE relative to PC.