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 y...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-11, Vol.281 (46), p.34870-34879
Main Authors: Meley, Daniel, Bauvy, Chantal, Houben-Weerts, Judith H.P.M., Dubbelhuis, Peter F., Helmond, Mariette T.J., Codogno, Patrice, Meijer, Alfred J.
Format: Article
Language:English
Subjects:
Aminoimidazole Carboxamide
Aminoimidazole Carboxamide - analogs & derivatives
Aminoimidazole Carboxamide - pharmacology
AMP-Activated Protein Kinases
Animals
Autophagy
Autophagy - drug effects
Autophagy - physiology
Cellular Biology
HeLa Cells
Hepatocytes
Hepatocytes - drug effects
Hepatocytes - metabolism
HT29 Cells
Humans
Life Sciences
Male
Multienzyme Complexes
Multienzyme Complexes - antagonists & inhibitors
Multienzyme Complexes - genetics
Multienzyme Complexes - metabolism
Protein-Serine-Threonine Kinases
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Pyrazoles
Pyrazoles - pharmacology
Pyrimidines
Pyrimidines - pharmacology
Rats
Rats, Wistar
Ribonucleotides
Ribonucleotides - pharmacology
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M605488200