title: CCCP induces autophagy in an AMPK-independent manner.
abstract: AMP-activated protein kinase (AMPK) is an important sensor of cellular energy status, and is involved in cell growth and autophagy through mammalian target of rapamycin complex 1 (mTORC1). Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, leads to AMPK activation and Parkin-dependent mitophagy, respectively. However, the detailed biochemical mechanism of how CCCP induces autophagy or mitophagy has not been investigated yet. Here, we showed that CCCP inhibits mTORC1 independently of AMPK, although CCCP induces AMPK activation. Using wild type (WT) and AMPKα1/α2 double knockout (DKO) MEFs, we observed that CCCP promotes endogenous LC3 lipidation and formation of RFP-LC3 puncta, indicating autophagosome or autolysosome, in an AMPK-independent manner. Finally, we also revealed that the percentage of CCCP-dependent colocalization between mitochondria and RFP-LC3 puncta is similar both in WT and AMPKα1/α2 DKO MEFs. Based on these data, we concluded that AMPK is not essential in regulation of CCCP-induced autopahgy including mitophagy.
authors: Laboratory of Molecular Biology, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors: Kyum-Yil
authors: KY
authors: Kwon
authors: Benoit
authors: B
authors: Viollet
authors: Ook Joon
authors: OJ
authors: Yoo
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011494:Protein Kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases