Amino acids and mTORC1: from lysosomes to disease.

Trends Mol Med
Authors
Keywords
Abstract

The mechanistic target of rapamycin (mTOR) kinase controls growth and metabolism, and its deregulation underlies the pathogenesis of many diseases, including cancer, neurodegeneration, and diabetes. mTOR complex 1 (mTORC1) integrates signals arising from nutrients, energy, and growth factors, but how exactly these signals are propagated await to be fully understood. Recent findings have placed the lysosome, a key mediator of cellular catabolism, at the core of mTORC1 regulation by amino acids. A multiprotein complex that includes the Rag GTPases, Ragulator, and the v-ATPase forms an amino acid-sensing machinery on the lysosomal surface that affects the decision between cell growth and catabolism at multiple levels. The involvement of a catabolic organelle in growth signaling may have important implications for our understanding of mTORC1-related pathologies.

Year of Publication
2012
Journal
Trends Mol Med
Volume
18
Issue
9
Pages
524-33
Date Published
2012 Sep
ISSN
1471-499X
URL
DOI
10.1016/j.molmed.2012.05.007
PubMed ID
22749019
PubMed Central ID
PMC3432651
Links
Grant list
R01 CA103866 / CA / NCI NIH HHS / United States
R01 CA129105 / CA / NCI NIH HHS / United States
R37 AI047389 / AI / NIAID NIH HHS / United States
Howard Hughes Medical Institute / United States