Mitochondrial electron transport chain complex III is required for antimycin A to inhibit autophagy.


Ma, Xiuquan; Jin, Mingzhi; Cai, Yu; Xia, Hongguang; Long, Kai; Liu, Junli; Yu, Qiang; Yuan, Junying

Publication Year 2011
Journal Chemistry & Biology
Pages 1474-1481
Volume 18
Issue 11
PMID 22118681.0
PMCID PMC3225892
DOI 10.1016/j.chembiol.2011.08.009

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. Copyright © 2011 Elsevier Ltd. All rights reserved.