Amino acids and mTORC1: from lysosomes to disease
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Sabatini_Amino acids.pdf
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1.34 MB
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103210ef26274ba257122e86870278ae
Author(s) • •
Efeyan, Alejo
Zoncu, Roberto
Sabatini, David
Date Issued
September 2012
Journal
Trends in Molecular Medicine
Publisher
Elsevier
Citation
Efeyan, Alejo, Roberto Zoncu, and David M. Sabatini. “Amino Acids and mTORC1: From Lysosomes to Disease.” Trends in Molecular Medicine 18.9 (2012): 524–533.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.molmed.2012.05.007