Regulation of macroautophagy by mTOR and Beclin 1 complexes

Biochimie. 2008 Feb;90(2):313-23. doi: 10.1016/j.biochi.2007.08.014. Epub 2007 Sep 8.

Abstract

Macroautophagy or autophagy is a vacuolar degradative pathway terminating in the lysosomal compartment after forming a cytoplasmic vacuole or autophagosome that engulfs macromolecules and organelles. The original discovery that ATG (AuTophaGy related) genes in yeast are involved in the formation of autophagosomes has greatly increased our knowledge of the molecular basis of autophagy, and its role in cell function that extends far beyond non-selective degradation. The regulation of autophagy by signaling pathways overlaps the control of cell growth, proliferation, cell survival and death. The evolutionarily conserved TOR (Target of Rapamycin) kinase complex 1 plays an important role upstream of the Atg1 complex in the control of autophagy by growth factors, nutrients, calcium signaling and in response to stress situations, including hypoxia, oxidative stress and low energy. The Beclin 1 (Atg6) complex, which is involved in the initial step of autophagosome formation, is directly targeted by signaling pathways. Taken together, these data suggest that multiple signaling checkpoints are involved in regulating autophagosome formation.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Autophagy*
  • Beclin-1
  • Membrane Proteins / metabolism*
  • Protein Kinases / metabolism*
  • Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • TOR Serine-Threonine Kinases

Substances

  • Apoptosis Regulatory Proteins
  • Beclin 1 protein, S cerevisiae
  • Beclin-1
  • Becn1 protein, mouse
  • Membrane Proteins
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse