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Trends Mol Med. 2012 Sep;18(9):524-33. doi: 10.1016/j.molmed.2012.05.007. Epub 2012 Jun 28.

Amino acids and mTORC1: from lysosomes to disease.

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1
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

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.

PMID:
22749019
PMCID:
PMC3432651
DOI:
10.1016/j.molmed.2012.05.007
[Indexed for MEDLINE]
Free PMC Article
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