Fig. 3.

Glutamine and mTORC1. In the Rag-dependent pathway, glutamine is activated by the action of GLS1 or GLS2 to produce glutamate, which in turn can generate α-KG and, together with leucine acquired from glutamine exchange through LAT1, induces Rag-mediated recruitment of mTORC1 to the lysosomal surface. When glutamine catabolism is inactivated, tumor cells can synthesize glutamate via ASNS-mediated glutamine conversion, which in turn can generate ATP, thereby inhibiting the AMPK pathway and completely activating mTORC1 on the lysosomal surface, a process mediated by the mTORC1 coactivator Rheb. Moreover, glutamine can also regulate mTORC1 in a non-Rag-dependent manner via Arf1