4.1 Article

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

期刊

CHEMISTRY & BIOLOGY
卷 18, 期 11, 页码 1474-1481

出版社

CELL PRESS
DOI: 10.1016/j.chembiol.2011.08.009

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资金

  1. NIH, US
  2. National Institute on Aging (US) [PO1 AG027916]
  3. National Natural Science Foundation of China [31129004, 31000619]
  4. Shanghai Science and Technology Research Grants [08DZ1971403, 09JC1416700]
  5. China National Science & Technology Key Project [2012CB910704]

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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 He La 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.

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