The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates 
environmental and intracellular signals to regulate cell growth. Amino acids 
stimulate mTORC1 activation at the lysosome in a manner thought to be dependent 
on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and 
the vacuolar H(+)-adenosine triphosphatase (v-ATPase). We report that leucine 
and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent 
mechanisms, respectively. Glutamine promoted mTORC1 translocation to the 
lysosome in RagA and RagB knockout cells and required the v-ATPase but not the 
Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation 
factor-1 GTPase to be required for mTORC1 activation and lysosomal localization 
by glutamine. Our results uncover a signaling cascade to mTORC1 activation 
independent of the Rag GTPases and suggest that mTORC1 is differentially 
regulated by specific amino acids.