How Lysosomes Sense, Integrate, and Cope with Stress

Lysosomes are in the center of the cellular control of catabolic and anabolic processes. These membrane-surrounded acidic organelles contain around 70 hydrolases, 200 membrane proteins, and numerous accessory proteins associated with the cytosolic surface of lysosomes. Accessory and transmembrane proteins assemble in signaling complexes that sense and integrate multiple signals and transmit the information to the nucleus. This communication allows cells to respond to changes in multiple environmental conditions, including nutrient levels, pathogens, energy availability, and lysosomal damage, with the goal of restoring cellular homeostasis. This review summarizes our current understanding of the major molecular players and known pathways that are involved in control of metabolic and stress responses that either originate from lysosomes or regulate lysosomal functions.