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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
Volume18
Issue9
Pages524-33
Date Published2012 Sep
ISSN1471-499X
KeywordsAmino Acids, Diabetes Mellitus, Humans, Lysosomes, Multiprotein Complexes, Neoplasms, Neurodegenerative Diseases, TOR Serine-Threonine Kinases
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1471-4914(12)00093-7
DOI10.1016/j.molmed.2012.05.007
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22749019?dopt=Abstract

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