Amino acids and mTORC1: from lysosomes to disease.
Authors | |
Keywords | |
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. |
Year of Publication | 2012
|
Journal | Trends Mol Med
|
Volume | 18
|
Issue | 9
|
Pages | 524-33
|
Date Published | 2012 Sep
|
ISSN | 1471-499X
|
URL | |
DOI | 10.1016/j.molmed.2012.05.007
|
PubMed ID | 22749019
|
PubMed Central ID | PMC3432651
|
Links | |
Grant list | R01 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
|