Proton leakage across lipid bilayers: Oxygen atoms of phospholipid ester linkers align water molecules into transmembrane water wires

• Published in: Biochimica et biophysica acta. Bioenergetics 2019-06, Vol.1860 (6), p.439-451
• Main Authors: Bozdaganyan, Marine E., Lokhmatikov, Alexey V., Voskoboynikova, Natalia, Cherepanov, Dmitry A., Steinhoff, Heinz-Jürgen, Shaitan, Konstantin V., Mulkidjanian, Armen Y.
• Format: Article
• Language: English
• Subjects: Bioenergetics; Chemiosmotic coupling; Ester lipids; Ether lipids; Lipid ester linkers; Mitochondria; Proton permeability; Proton potential
• ISSN: 0005-2728; 1879-2650
• DOI: 10.1016/j.bbabio.2019.03.001

Up to half of the cellular energy gets lost owing to membrane proton leakage. The permeability of lipid bilayers to protons is by several orders of magnitude higher than to other cations, which implies efficient proton-specific passages. The nature of these passages remains obscure. By combining experimental measurements of proton flow across phosphatidylcholine vesicles, steered molecular dynamics (MD) simulations of phosphatidylcholine bilayers and kinetic modelling, we have analyzed whether protons could pass between opposite phospholipid molecules when they sporadically converge. The MD simulations showed that each time, when the phosphorus atoms of the two phosphatidylcholine molecules got closer than 1.6 nm, the eight oxygen atoms of their ester linkages could form a transmembrane ‘oxygen passage’ along which several water molecules aligned into a water wire. Proton permeability along such water wires would be limited by rearrangement of oxygen atoms, which could explain the experimentally shown independence of the proton permeability of pH, H2O/D2O substitution, and membrane dipole potential. We suggest that protons can cross lipid bilayers by moving along short, self-sustaining water wires supported by oxygen atoms of lipid ester linkages. [Display omitted] •Up to half of the cellular energy gets lost owing to membrane proton leakage.•The mechanism of proton passage across lipid bilayers has remained obscure.•We have analyzed whether protons could pass between opposite phospholipid molecules when they sporadically converge.•When the phosphorus atoms of the two lipid molecules get closer than 1.6 nm, oxygen atoms of their ester linkers build a transmembrane “oxygen passage”.•Water molecules align in a proton-conducting water wire along the oxygen atoms of lipids.