Scientists have discovered that lysosomes — the cell's recycling centers — don't just pull protons from the surrounding cytoplasm to stay acidic. Instead, mitochondria physically dock against lysosomes and pump protons directly into them through membrane contact sites. When these contacts are lost during aging or cellular senescence, lysosomes become less acidic and stop working properly. Restoring the contacts with an engineered protein linker rescued lysosome acidity and autophagy. In senescent human cells, preserving lysosome acidification reduced the secretion of inflammatory SASP factors. This mechanism is conserved from yeast to humans, reshaping how scientists understand lysosomal function and its decline in aging.
