title: Amino acids and mTORC1: from lysosomes to disease.
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.
authors: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
authors: Alejo
authors: A
authors: Efeyan
authors: Roberto
authors: R
authors: Zoncu
authors: David M
authors: DM
authors: Sabatini
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases