Role of AMP-activated protein kinase in autophagy and proteasome function.
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.
Viana
Rosa
R
Instituto de Biomedicina de Valencia, CSIC, Nutrient signaling, Jaime Roig 11, 46010 Valencia, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), Valencia, Spain.
Aguado
Carmen
C
Esteban
Inmaculada
I
Moreno
Daniel
D
Viollet
Benoit
B
Knecht
Erwin
E
Sanz
Pascual
P
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000201:enzymology
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D017346:Protein Serine-Threonine Kinases; D012263:Ribonucleosides; C491997:BECN1 protein, human; C011651:acadesine