The lysosome plays a key role in cellular homeostasis by controlling both 
cellular clearance and energy production to respond to environmental cues. 
However, the mechanisms mediating lysosomal adaptation are largely unknown. 
Here, we show that the Transcription Factor EB (TFEB), a master regulator of 
lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 
(mTORC1) on the lysosomal membrane. When nutrients are present, phosphorylation 
of TFEB by mTORC1 inhibits TFEB activity. Conversely, pharmacological inhibition 
of mTORC1, as well as starvation and lysosomal disruption, activates TFEB by 
promoting its nuclear translocation. In addition, the transcriptional response 
of lysosomal and autophagic genes to either lysosomal dysfunction or 
pharmacological inhibition of mTORC1 is suppressed in TFEB-/- cells. 
Interestingly, the Rag GTPase complex, which senses lysosomal amino acids and 
activates mTORC1, is both necessary and sufficient to regulate starvation- and 
stress-induced nuclear translocation of TFEB. These data indicate that the 
lysosome senses its content and regulates its own biogenesis by a 
lysosome-to-nucleus signalling mechanism that involves TFEB and mTOR.