AMP-activated protein kinase and the regulation of autophagic proteolysis.
Interruption of mTOR-dependent signaling by rapamycin is known to stimulate autophagy, both in mammalian cells and in yeast. Because activation of AMPK also inhibits mTOR-dependent signaling one would expect stimulation of autophagy by AMPK activation. According to the literature, this is true for yeast but, unexpectedly, not for mammalian cells on the basis of the use of AICAR, a pharmacological activator of AMPK. In the present study, carried out with hepatocytes, HT-29 cells, and HeLa cells, we have reexamined the possible role of AMPK in the control of mammalian autophagy. Inhibition of AMPK activity by compound C or by transfection with a dominant negative form of AMPK almost completely inhibited autophagy. These results suggest that the inhibition of autophagy by AICAR is not related to its ability to activate AMPK. We conclude that in mammalian cells, as in yeast, AMPK is required for autophagy.
Meley
Daniel
D
INSERM U756, Faculté de Pharmacie, Université Paris-Sud 11, 92296 Châtenay-Malabry, France.
Bauvy
Chantal
C
Houben-Weerts
Judith H P M
JH
Dubbelhuis
Peter F
PF
Helmond
Mariette T J
MT
Codogno
Patrice
P
Meijer
Alfred J
AJ
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D019073:HT29 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology
D009097:Multienzyme Complexes; D011720:Pyrazoles; D011743:Pyrimidines; D012265:Ribonucleotides; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide