title: CCCP-Induced LC3 lipidation depends on Atg9 whereas FIP200/Atg13 and Beclin 1/Atg14 are dispensable.
abstract: Treatment of cells with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial proton gradient uncoupler, can result in mitochondrial damage and autophagy activation, which in turn eliminates the injured mitochondria in a Parkin-dependent way. How CCCP mobilizes the autophagy machinery is not fully understood. By analyzing a key autophagy step, LC3 lipidation, we examined the roles of two kinase complexes typically involved in the initiation and nucleation phases of autophagy, namely the ULK kinase complex (UKC) and the Beclin 1/Atg14 complex. We found that CCCP-induced LC3 lipidation could be independent of Beclin 1 and Atg14. In addition, deletion or knockdown of the UKC component FIP200 or Atg13 only led to a partial reduction in LC3 lipidation, indicating that UKC could be also dispensable for this step during CCCP treatment. In contrast, Atg9, which is important for transporting vesicles to early autophagosomal structure, was required for CCCP-induced LC3 lipidation. Taken together, these data suggest that CCCP-induced autophagy and mitophagy depends more critically on Atg9 vesicles than on UKC and Beclin 1/Atg14 complex.
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors: Daohong
authors: D
authors: Chen
authors: Xi
authors: X
authors: Chen
authors: Min
authors: M
authors: Li
authors: Hao
authors: H
authors: Zhang
authors: Wen-Xing
authors: WX
authors: Ding
authors: Xiao-Ming
authors: XM
authors: Yin
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology*; D033921:Vesicular Transport Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; C549015:Atg9A protein, mouse; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C480860:Map1lc3b protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C428743:Rb1cc1 protein, mouse; D014475:Uncoupling Agents; D033921:Vesicular Transport Proteins; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone
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