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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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106904 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826211473912758272 |
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| author | Efeyan, Alejo Zoncu, Roberto Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Efeyan, Alejo Zoncu, Roberto Sabatini, David |
| author_sort | Efeyan, Alejo |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:06:30Z |
| format | Article |
| id | mit-1721.1/106904 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:06:30Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1069042022-10-02T00:39:14Z Amino acids and mTORC1: from lysosomes to disease Efeyan, Alejo Zoncu, Roberto Sabatini, David Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Efeyan, Alejo Zoncu, Roberto Sabatini, David 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. National Institutes of Health (U.S.) (Grants R01 CA129105, R01 CA103866, and R37 AI047389) American Federation for Aging Research Starr Foundation David H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Program Ellison Medical Foundation Jane Coffin Childs Memorial Fund for Medical Research (Fellowship) LAM Foundation Human Frontier Science Program (Strasbourg, France) 2017-02-10T19:20:14Z 2017-02-10T19:20:14Z 2012-09 Article http://purl.org/eprint/type/JournalArticle 1471-4914 http://hdl.handle.net/1721.1/106904 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. https://orcid.org/0000-0002-1446-7256 en_US https://dx.doi.org/10.1016/j.molmed.2012.05.007 Trends in Molecular Medicine Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Efeyan, Alejo Zoncu, Roberto Sabatini, David Amino acids and mTORC1: from lysosomes to disease |
| title | Amino acids and mTORC1: from lysosomes to disease |
| title_full | Amino acids and mTORC1: from lysosomes to disease |
| title_fullStr | Amino acids and mTORC1: from lysosomes to disease |
| title_full_unstemmed | Amino acids and mTORC1: from lysosomes to disease |
| title_short | Amino acids and mTORC1: from lysosomes to disease |
| title_sort | amino acids and mtorc1 from lysosomes to disease |
| url | http://hdl.handle.net/1721.1/106904 https://orcid.org/0000-0002-1446-7256 |
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