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In a previous work, we have shown that a spatially localized transmembrane pHgradient, produced by acid micro-injection near the external side ofcardiolipin-containing giant unilamellar vesicles, leads to the formation oftubules that retract after the dissipation of this gradient. These tubules havemorphologies similar to mitochondrial cristae. The tubulation effect is due todirect phospholipid packing modification in the outer leaflet that is promotedby protonation of cardiolipin headgroups. Here we compare the case ofcardiolipin-containing giant unilamellar vesicles with that ofphosphatidylglycerol-containing giant unilamellar vesicles. Local acidificationalso promotes formation of tubules in the latter. However, compared tocardiolipin-containing giant unilamellar vesicles the tubules are longer,exhibit a visible pearling and have a much longer lifetime after acidmicro-injection is stopped. We attribute these differences to an additionalmechanism that increases monolayer surface imbalance, namely inward PGflip-flop promoted by the local transmembrane pH-gradient. Simulations using afully non-linear membrane model as well as geometrical calculations are inagreement with this hypothesis. Interestingly, among yeast mutants deficient incardiolipin biosynthesis, only the crd1-null mutant, which accumulatesphosphatidylglycerol, displays significant mitochondrial activity. Our workprovides a possible explanation of such a property and further emphasizes thesalient role of specific lipids in mitochondrial function.

biophysical journal

Interplay of packing and flip-flop in local bilayer deformation. How  phosphatidylglycerol could rescue mitochondrial function in a  cardiolipin-deficient yeast mutant