mTOR and autophagy: a dynamic relationship governed by nutrients and energy

Semin Cell Dev Biol. 2014 Dec;36:121-9. doi: 10.1016/j.semcdb.2014.08.006. Epub 2014 Aug 23.

Abstract

Mechanistic target of rapamycin (mTOR) functions as a key homeostatic regulator of cell growth and orchestrates whether anabolic or catabolic reactions are favoured. mTOR complex 1 (mTORC1) manages multiple biosynthetic pathways and promotes cell growth when nutrients are in plentiful supply. Many advances have been made over the last decade on nutrient sensing centred on mTORC1. Recent research reveals that mTORC1 maintains nutrient homeostasis through lysosomal biogenesis and autophagic processes. Cells utilise autophagy to recycle damaged or unwanted organelles and macromolecules and in so doing, generate energy and recover precursor building blocks necessary for normal growth. It is clear that mTOR and autophagy are closely integrated within cells, where defects in signalling through both pathways are known to drive the onset of a range of human diseases, such as cancer and neurodegenerative disease. This review focuses on the dynamic signalling interplay between mTOR and autophagy, which is governed by a core set of proteins that sense nutrients at lysosomal membranes.

Keywords: Autophagy; Lysosome; Nutrient; ULK1; VPS34; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Autophagy / physiology*
  • Autophagy-Related Protein-1 Homolog
  • Cell Membrane / metabolism*
  • Class III Phosphatidylinositol 3-Kinases / metabolism
  • Energy Metabolism / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lysosomes / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Phosphatidylinositols / metabolism
  • Phospholipids / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Phosphatidylinositols
  • Phospholipids
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Class III Phosphatidylinositol 3-Kinases
  • Autophagy-Related Protein-1 Homolog
  • Mechanistic Target of Rapamycin Complex 1
  • Protein-Serine-Threonine Kinases
  • ULK1 protein, human
  • AMP-Activated Protein Kinases