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Trends Mol Med DOI:10.1016/j.molmed.2012.05.007

Amino acids and mTORC1: from lysosomes to disease.

Publication TypeJournal Article
Year of Publication2012
AuthorsEfeyan, A, Zoncu, R, Sabatini, DM
JournalTrends Mol Med
Date Published2012 Sep
KeywordsAmino Acids, Diabetes Mellitus, Humans, Lysosomes, Multiprotein Complexes, Neoplasms, Neurodegenerative Diseases, TOR Serine-Threonine Kinases

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.


Alternate JournalTrends Mol Med
PubMed ID22749019
PubMed Central IDPMC3432651
Grant ListR01 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