mTOR integrates amino acid- and energy-sensing pathways

Biochem Biophys Res Commun. 2004 Jan 9;313(2):443-6. doi: 10.1016/j.bbrc.2003.07.019.


The AMP-activated protein kinase (AMPK) exists as a heterotrimetric complex comprising a catalytic alpha subunit and non-catalytic beta and gamma subunits. Under conditions of hypoxia, exercise, ischemia, heat shock, and low glucose, AMPK is activated allosterically by rising cellular AMP and by phosphorylation of the catalytic alpha subunit. The mammalian target of rapamycin (mTOR) controls cellular functions in response to amino acids and growth factors. Recent reports including our study have demonstrated the possible interplay between mTOR and AMPK signaling pathways, supporting a model in which mitochondrial dysfunction caused by the mitochondrial inhibitors or ATP depletion inhibits activation of p70 S6 kinase alpha (p70alpha), a downstream effector of mTOR, by activating AMPK. Leucine may stimulate p70alpha phosphorylation via mTOR pathway, in part, by serving both as a mitochondrial fuel through oxidative carboxylation and an allosteric activation of glutamate dehydrogenase. This hypothesis may support an idea in which leucine modulates mTOR function, in part by regulating mitochondrial function and AMPK. Further understanding of the role of mTOR in coordinating amino acid- and energy-sensing pathways would provide new insights into relationship between nutrients and cellular functions.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases
  • Amino Acids / metabolism*
  • Animals
  • Energy Metabolism / physiology*
  • Glucose / metabolism
  • Humans
  • Leucine / metabolism
  • Mitochondria / metabolism
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases


  • Amino Acids
  • Multienzyme Complexes
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Leucine
  • Glucose