Mitochondrial Electron Transport Chain Complex III Is Required for Antimycin A to Inhibit Autophagy

SummaryAutophagy 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.

► Antimycin A can inhibit autophagy
► The activity of antimycin A as an inhibitor of mETC complex III correlates with its activity in inhibiting autophagy
► Antimycin A and myxothiazol cannot inhibit autophagy in mtDNA-depleted cells