mTORC1 Signaling

More Than a Proton Pump

Science Signaling  08 Nov 2011:
Vol. 4, Issue 198, pp. ec312
DOI: 10.1126/scisignal.4198ec312

When cells are running low on amino acids, they can activate autophagy to digest existing cellular components, but it has been unclear how the depletion of amino acids is sensed. The mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of this process and, when amino acids are present, becomes localized to lysosomes and inhibits autophagy. Zoncu et al. (see the Perspective by Abrahamsen and Stenmark) used small interfering RNA techniques to search for lysosomal components necessary for mTORC1 signaling. The vacuolar H+-adenosine triphosphatase, which functions to acidify lysosomes, was found also to be necessary for sensing of amino acids within the lysosome. The protein directly interacted in an amino acid–dependent manner with proteins associated with mTORC1.

R. Zoncu, L. Bar-Peled, A. Efeyan, S. Wang, Y. Sancak, D. M. Sabatini, mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H+-ATPase. Science 334, 678–683 (2011). [Abstract] [Full Text]

H. Abrahamsen, H. Stenmark, Growth signaling from inside. Science 334, 611–612 (2011). [Abstract] [Full Text]