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PreprintCC BYbioRxiv

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

Abstract

Cardiolipin (CL) is a phospholipid found in the inner mitochondrial membrane (IMM) where it increases the efficiency of ATP regeneration. We have investigated the hypothesis that this increase may result in part from CL concentrating H+ at the IMM surface through electrostatic interactions as the CL polar head is a dianion at physiological pH. To this aim, we compared the concentrations and movements of H+ at the surface of giant planar phosphatidylcholine (PC) membranes and 20% CL enriched PC membranes by recording their surface pH with the membrane-grafted pH probe fluorescein DHPE. CL enrichment of the membranes increased their surface H+ activity by a ~4 factor. Moreover, we observed non-gaussian spatial H+ concentration profiles with distance from a point H+ source with both PC and CL membranes suggesting that both lipids also induce interactions between probe molecules. A whole bath pH variation revealed that these interactions allow the traveling of reversible acidification fronts with constant speed over the membrane between high and low pH states. A reaction-diffusion model of these observations suggests that membranes support these fronts through a mechanism of autocatalytic (de)protonation of the membrane surface. In mitochondria, these fronts would result in transitions between high and low pH states, the low one having a larger H+ concentration in CL-enriched regions of the IMM. Such an increase at the inner leaflet of the IMM may increase efficiency of the respiratory chain whereas the increase at the outer leaflet may boost the ATP synthase rate.

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BibTeX
@misc{baroudi2026cardiolipin,
  title = {{Cardiolipin increases the peak of reversible traveling H+ fronts at the membrane surface}},
  author = {N.-B. Baroudi and S. G. Kruglik and P. Lopez and S. Haliyo and S. Genet},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.15.744977},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.15.744977v2},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Cardiolipin increases the peak of reversible traveling H+ fronts at the membrane surface
AU  - N.-B. Baroudi
AU  - S. G. Kruglik
AU  - P. Lopez
AU  - S. Haliyo
AU  - S. Genet
PY  - 2026
DA  - 2026/08/15
PB  - bioRxiv
DO  - 10.64898/2026.08.15.744977
UR  - https://www.biorxiv.org/content/10.64898/2026.08.15.744977v2
AB  - Cardiolipin (CL) is a phospholipid found in the inner mitochondrial membrane (IMM) where it increases the efficiency of ATP regeneration. We have investigated the hypothesis that this increase may result in part from CL concentrating H+ at the IMM surface through electrostatic interactions as the CL polar head is a dianion at physiological pH. To this aim, we compared the concentrations and movements of H+ at the surface of giant planar phosphatidylcholine (PC) membranes and 20% CL enriched PC membranes by recording their surface pH with the membrane-grafted pH probe fluorescein DHPE. CL enrichment of the membranes increased their surface H+ activity by a ~4 factor. Moreover, we observed non-gaussian spatial H+ concentration profiles with distance from a point H+ source with both PC and CL membranes suggesting that both lipids also induce interactions between probe molecules. A whole bath pH variation revealed that these interactions allow the traveling of reversible acidification fronts with constant speed over the membrane between high and low pH states. A reaction-diffusion model of these observations suggests that membranes support these fronts through a mechanism of autocatalytic (de)protonation of the membrane surface. In mitochondria, these fronts would result in transitions between high and low pH states, the low one having a larger H+ concentration in CL-enriched regions of the IMM. Such an increase at the inner leaflet of the IMM may increase efficiency of the respiratory chain whereas the increase at the outer leaflet may boost the ATP synthase rate.
ER  -