Mitochondrial electron transport chain complex III is required for antimycin A to inhibit autophagy.
Mitochondrial electron transport chain complex III is required for antimycin A to inhibit autophagy.
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DOI：
10.1016/j.chembiol.2011.08.009
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发表时间：
2011-11-23
影响因子：
--
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Ma X;Jin M;Cai Y;Xia H;Long K;Liu J;Yu Q;Yuan J
自噬是一种细胞溶酶体依赖的分解代谢机制，介导胞内细胞器和长寿命蛋白质的周转。自噬功能障碍与多种人类疾病有关。鉴定哺乳动物细胞中新的自噬因子对于理解这一复杂的细胞通路如何应对广泛的挑战非常重要。在这里，我们报道线粒体电子传递链（mETC）复合物III在自噬诱导中起作用。我们发现抗霉素A，一种已知的mETC复合物III的抑制剂，可以抑制自噬。一项结构和功能研究表明，抗霉素A的四种相似类似物对线粒体抑制没有影响，也不抑制自噬；而另一种与抗霉素A结构无关的mETC复合物III抑制剂myxothiazol则抑制自噬。此外，抗霉素A和粘噻唑不能抑制mtdna缺失的H4和mtdna缺失的HeLa细胞的自噬。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复合体III可能在介导自噬诱导中起作用。
Autophagy is a cellular lysosome-dependent catabolic mechanism mediating the turnover of intracellular organelles and long-lived proteins. Dysfunction of autophagy has been implicated in multiple human diseases. Identification of novel autophagy factors in mammalian cells is important for understanding how this complex cellular pathway responds to a broad range of challenges. Here we report that mitochondrial electron transport chain (mETC) complex III plays a role in autophagy induction. 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; while 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.
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影响因子：
56.9
作者：
Dennis, PB;Jaeschke, A;Thomas, G
通讯作者：
Thomas, G
影响因子：
21.3
作者：
Hayashi-Nishino, Mitsuko;Fujita, Naonobu;Yamamoto, Akitsugu
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DOI：
10.1073/pnas.1009485107
发表时间：
2010-08-10
影响因子：
11.1
作者：
Lipinski, Marta M.;Zheng, Bin;Yuan, Junying
通讯作者：
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影响因子：
64.5
作者：
Hailey DW;Rambold AS;Satpute-Krishnan P;Mitra K;Sougrat R;Kim PK;Lippincott-Schwartz J
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影响因子：
3.3
作者：
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通讯作者：
Klionsky DJ