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	MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential
	Sun, Chao1,2,3; Liu, Xiongxiong1,2,3; Di, Cuixia1,2,3; Wang, Zhenhua4; Mi, Xiangquan5; Liu, Yang1,2,3; Zhao, Qiuyue1,2,3; Mao, Aihong1,2,3; Chen, Weiqiang1,2,3; Gan, Lu1,2,3
刊名	AUTOPHAGY
	2017
卷号	13期号:4页码:730-738
关键词	autophagy energy metabolism MitoQ proton displacement pseudo-MMP
ISSN号	1554-8627
DOI	10.1080/15548627.2017.1280219
通讯作者	Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要	During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways.
收录类别	SCI
WOS关键词	TARGETED ANTIOXIDANT MITOQ ; CELL-DEATH ; PROTON TRANSLOCATION ; PANCREATIC-CANCER ; ATP ; METABOLISM ; ACTIVATION ; UBIQUINONE ; MECHANISM ; THERAPY
WOS研究方向	Cell Biology
WOS类目	Cell Biology
语种	英语
出版者	TAYLOR & FRANCIS INC
WOS记录号	WOS:000399338800008
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2558007
专题	寒区旱区环境与工程研究所
通讯作者	Zhang, Hong
作者单位	1.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Med, Lanzhou, Peoples R China 3.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou, Peoples R China 4.Yantai Univ, Coll Life Sci, Yantai, Peoples R China 5.Lanzhou Univ, Coll Life Sci, Lanzhou, Peoples R China 6.Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou, Peoples R China
推荐引用方式 GB/T 7714	Sun, Chao,Liu, Xiongxiong,Di, Cuixia,et al. MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential[J]. AUTOPHAGY,2017,13(4):730-738.
APA	Sun, Chao.,Liu, Xiongxiong.,Di, Cuixia.,Wang, Zhenhua.,Mi, Xiangquan.,...&Zhang, Hong.(2017).MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.AUTOPHAGY,13(4),730-738.
MLA	Sun, Chao,et al."MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential".AUTOPHAGY 13.4(2017):730-738.

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