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MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential

文献类型：期刊论文

作者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
出版日期2017
卷号13页码:730-738
关键词autophagy energy metabolism MitoQ proton displacement pseudo-MMP
ISSN号1554-8627
DOI10.1080/15548627.2017.1280219
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.
WOS关键词TARGETED ANTIOXIDANT MITOQ ; CELL-DEATH ; PROTON TRANSLOCATION ; PANCREATIC-CANCER ; ATP ; METABOLISM ; ACTIVATION ; UBIQUINONE ; MECHANISM ; THERAPY
资助项目National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11505245] ; National Key projects of Research and Development[2016YFC0904600] ; Western Talents Program of the Chinese Academy of Sciences[Y460040XB0]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000399338800008
出版者TAYLOR & FRANCIS INC
资助机构National Natural Science Foundation of China ; National Key projects of Research and Development ; Western Talents Program of the Chinese Academy of Sciences
源URL[http://119.78.100.186/handle/113462/44658]  
专题中国科学院近代物理研究所
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,2017,13:730-738.
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,13,730-738.
MLA Sun, Chao,et al."MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential".AUTOPHAGY 13(2017):730-738.

入库方式： OAI收割

来源：近代物理研究所

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