Amino acids and mTORC1: from lysosomes to disease

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 ho...

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Bibliographic Details
Published in:Trends in molecular medicine 2012-09, Vol.18 (9), p.524-533
Main Authors: Efeyan, Alejo, Zoncu, Roberto, Sabatini, David M
Format: Article
Language:English
Subjects:
Amino Acids - metabolism
Diabetes Mellitus - metabolism
Humans
Lysosomes - metabolism
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Neoplasms - metabolism
Neurodegenerative Diseases - metabolism
Pathology
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
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Summary: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.
ISSN:1471-4914
1471-499X
DOI:10.1016/j.molmed.2012.05.007