Mitochondria-lysosome coupling contributes to lysosome acidification and aging

The acidic pH inside the lysosome (vacuole in yeast) is essential for cellular content degradation, signaling, and autophagy. Defect in lysosome/vacuole acidification is a conserved hallmark of aging and age-related diseases.

Traditionally, lysosome/vacuole is thought to import free protons (H⁺) from the surrounding neutral cytosol. In this study, we uncovered a previously unrecognized, conserved lysosome/vacuole acidification mechanism, involving lysosomal/vacuolar uptake of H+ pumped out by mitochondrial electron transport chain through membrane contacts between mitochondria and lysosomes/vacuoles. Aging/senescence-associated disruption of mitochondria-lysosome/vacuole contacts causes lysosomal/vacuolar de-acidification, which can be reversed by expressing a linker to connect these organelles and through an asymmetry-dependent rejuvenation process in daughter cells.