Figure 3.

Rags coordinate lysosome biogenesis and autophagy induction at the lysosome surface. The Rag GTPases sense amino acid availability and serve as a signal integration hub for mTORC1 activation. Another small GTPase, Rheb, coordinates signaling in response to growth factor signals and cellular energy level cues via AKT and AMPK, which positively and negatively regulate Rheb through TSC. Under anabolic signaling conditions, mTORC1 activates protein synthesis through phosphorylation of intermediaries such as 4EBP1 and S6K. Under catabolic conditions, autophagy and lysosomal biogenesis is induced via de-repression of TFEB and TFE3 at the lysosome surface.