title: Mitochondrial electron transport chain complex III is required for antimycin A to inhibit autophagy.
abstract: Autophagy is a cellular lysosome-dependent catabolic mechanism mediating the turnover of intracellular organelles and long-lived proteins. We show that antimycin A, a known inhibitor of mETC complex III, can inhibit autophagy. A structural and functional study shows that four close analogs of antimycin A that have no effect on mitochondria inhibition also do not inhibit autophagy, whereas myxothiazol, another mETC complex III inhibitor with unrelated structure to antimycin A, inhibits autophagy. Additionally, antimycin A and myxothiazol cannot inhibit autophagy in mtDNA-depleted H4 and mtDNA-depleted HeLa cells. These data suggest that antimycin A inhibits autophagy through its inhibitory activity on mETC complex III. Our data suggest that mETC complex III may have a role in mediating autophagy induction.
authors: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-ling Road, Shanghai 200032, China.
authors: Xiuquan
authors: X
authors: Ma
authors: Mingzhi
authors: M
authors: Jin
authors: Yu
authors: Y
authors: Cai
authors: Hongguang
authors: H
authors: Xia
authors: Kai
authors: K
authors: Long
authors: Junli
authors: J
authors: Liu
authors: Qiang
authors: Q
authors: Yu
authors: Junying
authors: J
authors: Yuan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000968:Antimycin A; D000255:Adenosine Triphosphate; D014450:Electron Transport Complex III