Cardiolipin increases the peak of reversible traveling H+ fronts at the membrane surface

Cardiolipin (CL) is a phospholipid commonly found in the inner mitochondrial membrane (IMM) where it enhances the efficiency of ATP regeneration. Researchers examined the theory that this boost might be partially due to CL drawing H+ ions toward the IMM surface via electrostatic forces, as the CL molecule has a dianionic polar head at physiological pH levels.

To test this theory, the researchers compared the H+ concentrations and mobility on giant planar phosphatidylcholine (PC) membranes and CL-enriched PC membranes by measuring the surface pH with a fluorescein DHPE pH probe. The results showed that CL increased the surface H+ activity by approximately four times. Additionally, the researchers discovered non-Gaussian spatial H+ concentration patterns near a single H+ source on both PC and CL membranes, indicating that both lipids facilitate interactions between the probe molecules.

A bath pH variation experiment demonstrated that these interactions enable the propagation of reversible acidification fronts with a consistent speed across the membrane between high and low pH states. A reaction-diffusion model of these findings proposes that membranes facilitate these fronts through a process of autocatalytic protonation and deprotonation at the membrane surface.

In mitochondria, such fronts would lead to transitions between high and low pH states, with the low pH region containing a higher H+ concentration in CL-enriched areas of the IMM. This heightened H+ concentration at the inner leaflet of the IMM could potentially enhance the efficiency of the respiratory chain, while the increased H+ concentration at the outer leaflet might boost the rate of ATP synthesis.