Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is an important, highly 
conserved, regulator of cell growth. Ancient among the signals that regulate 
mTORC1 are nutrients. Amino acids direct mTORC1 to the surface of the late 
endosome/lysosome, where mTORC1 becomes receptive to other inputs. However, the 
interplay between endosomes and mTORC1 is poorly understood. Here, we report the 
discovery of a network that links mTORC1 to a critical component of the late 
endosome/lysosome, the V-ATPase. In an unbiased screen, we found that mTORC1 
regulated the expression of, among other lysosomal genes, the V-ATPases. mTORC1 
regulates V-ATPase expression both in cells and in mice. V-ATPase regulation by 
mTORC1 involves a transcription factor translocated in renal cancer, TFEB. TFEB 
is required for the expression of a large subset of mTORC1 responsive genes. 
mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and 
in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis. 
These data uncover a regulatory network linking an oncogenic transcription 
factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and 
endocytosis.