Fig. 1.

Mitochondrial proton leak and its role in cardiac aging. A Mitochondria pump protons through complexes I, III and IV to generate a proton gradient. Protons return to the matrix through complex V (ATPase, ATP synthase) to drive ATP production. Protons leak back to matrix through ANT1, UCPs and the mitochondrial inner membrane. B Aging increases the proton leak and concurrently reduces the tolerance to the potentially detrimental effects of proton leak. Basal proton leak is needed to maintain thermogenesis and other physiological processes. Mild increases in proton leak to mimic caloric restriction or exert a preconditioning effect may be beneficial. However, excessive proton leak may contribute to the pathogenesis of aging in the heart and contribute to pathologies in other organs