The voltage difference (ΔΨm) across the inner mitochondrial membrane, generated by the electron transport chain pumping protons from the mitochondrial matrix into the intermembrane space. This electrochemical gradient is the driving force for ATP synthesis—the cell’s primary energy currency.

Loss of mitochondrial membrane potential signals mitochondrial dysfunction and can trigger apoptosis. In aging and disease, membrane potential declines as the inner membrane’s lipid composition deteriorates—particularly the cardiolipin molecules that anchor electron transport chain complexes. SS-31 (Elamipretide) targets this specific vulnerability by binding to cardiolipin and stabilizing its structure, which is why the compound is in clinical trials for mitochondrial diseases including Barth syndrome and age-related macular degeneration.