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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.

SUBMITTER: Ma X 

PROVIDER: S-EPMC3225892 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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

Ma Xiuquan X   Jin Mingzhi M   Cai Yu Y   Xia Hongguang H   Long Kai K   Liu Junli J   Yu Qiang Q   Yuan Junying J  

Chemistry & biology 20111101 11


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.  ...[more]

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