Role of AMP-activated protein kinase in autophagy and proteasome function

Biochem Biophys Res Commun. 2008 May 9;369(3):964-8. doi: 10.1016/j.bbrc.2008.02.126. Epub 2008 Mar 6.

Abstract

In this work, we have examined the possible role of AMP-activated protein kinase (a key energy sensor) in regulating intracellular protein degradation. We have found that AICAR, a known activator of AMPK, has a dual effect. On one hand, it inhibits autophagy by a mechanism independent of AMPK activity; AICAR decreases class III PI3-kinase binding to beclin-1 and this effect counteracts and reverses the known positive effect of AMPK activity on autophagy. On the other hand, AICAR inhibits the proteasomal degradation of proteins by an AMPK-dependent mechanism. This is a novel function of AMPK that allows the regulation of proteasomal activity under conditions of energy demand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy* / drug effects
  • Beclin-1
  • Cells, Cultured
  • Down-Regulation
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Multienzyme Complexes / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ribonucleosides / pharmacology
  • Vacuoles / drug effects
  • Vacuoles / enzymology

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • Multienzyme Complexes
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteasome Inhibitors
  • Ribonucleosides
  • Aminoimidazole Carboxamide
  • acadesine
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Proteasome Endopeptidase Complex