Ma Xiuquan, Jin Mingzhi, Cai Yu, Xia Hongguang, Long Kai, Liu Junli, Yu Qiang, Yuan Junying
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.
Chem Biol. 2011 Nov 23;18(11):1474-81. 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.
自噬是一种细胞内依赖溶酶体的分解代谢机制，介导细胞内细胞器和长寿蛋白的周转。我们发现抗霉素A（一种已知的线粒体电子传递链（mETC）复合物III抑制剂）可以抑制自噬。一项结构和功能研究表明，抗霉素A的四种紧密类似物对线粒体抑制没有作用，也不抑制自噬，而粘噻唑（另一种与抗霉素A结构无关的mETC复合物III抑制剂）则抑制自噬。此外，抗霉素A和粘噻唑在mtDNA缺失的H4细胞和mtDNA缺失的HeLa细胞中均不能抑制自噬。这些数据表明，抗霉素A通过其对mETC复合物III的抑制活性来抑制自噬。我们的数据表明，mETC复合物III可能在介导自噬诱导中发挥作用。
