Fig. 1: Lysosomal function.

Lysosomes function as terminal sites of phagocytosis and autophagy and as cellular sensors and signaling hubs. Cargos are transported to lysosomes for degradation by the phagosome formed by the closure of reshaped plasma membrane during phagocytosis or the autophagosome formed by the closure of the phagophore in macroautophagy, directly swallowing into lysosomes through membrane indentation, protuberance, or the separation of the lysosomal membrane in microautophagy, and chaperone binding mainly through LAMP2A in CMA. Lysosomes also function as mTORC1 and AMPK signaling hubs. Under conditions of nutrient enrichment, Rag GTPases, heterodimers formed by RagA/B and RagC/D, are activated and tethered to the lysosomal membrane, further recruiting mTORC1. Rag GTPases can be activated by Ragulator and inhibited by the GATOR1 complex. Ragulator is activated by SLC38A and lysosomal V-ATPase, which stimulated by arginine and leucine in the lysosomal lumen, respectively, while the GATOR1 complex is inhibited by GATOR2, which is stimulated by amino acids in the cytoplasm. Then, mTORC1 is activated by Rheb GTPases stimulated by GF through the inhibition of TSC. Upon glucose deficiency, Axin causes the dissociation and inactivation of mTORC1 through the inhibition of Ragulator. In addition, Axin recruits AMPK by interacting with LKB1 and induces AMPK activation by forming complexes with V-ATPase and Ragulator.