CCCP-Induced LC3 lipidation depends on Atg9 whereas FIP200/Atg13 and Beclin 1/Atg14 are dispensable
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)
- Department of Pharmacology, Toxicology, and Therapeutics, the University of Kansas Medical Center, Kansas City, KS 66160 (United States)
Highlights: ► CCCP-induced LC3 lipidation can be independent of initiation/nucleation molecules. ► Atg9-mediated trafficking is critically required for CCCP-induced LC3 lipidation. ► CCCP-induced mitophagy may thus be more dependent on Atg9-positive vesicles. -- 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.
- OSTI ID:
- 22239507
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 432; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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