Figure 2.
Upstream nutrient signaling to mTORC1 and AMPK. Nutrient starvation results in the inactivation of mTORC1. Oxygen or nutrient deficiency can activate AMPK through ADP:AMP accumulation, negatively regulating mTORC1 through either AMPK-mediated phosphorylation of mTORC1 or activation of the upstream repressor TSC. Limited oxygen also upregulates hypoxia-responsive genes, which are capable of suppressing mTORC1 signaling through the activation of TSC or inhibition of Rheb. Amino-acid withdrawal or inactivation of the PI3K pathway inhibits mTORC1 signaling through negatively regulating the activation of mTORC1 at the lysosome by Rag GTPases and Rheb.
