Amino acids and mTORC1: from lysosomes to disease

Trends Mol Med. 2012 Sep;18(9):524-33. doi: 10.1016/j.molmed.2012.05.007. Epub 2012 Jun 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Amino Acids
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1