文献类型：期刊文献

英文题名：SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress

作者：Zhang, Mengli[1,2];Wu, Jian[3,4];Sun, Renqiang[1,2];Tao, Xiaoting[5,6];Wang, Xiaoxia[7];Kang, Qi[1,2];Wang, Hui[7];Zhang, Lei[1,2];Liu, Peng[1,2];Zhang, Jinye[1,2];Xia, Yukun[1,2];Zhao, Yuzheng[8];Yang, Yi[8];Xiong, Yue[1,2,9];Guan, Kun-Liang[1,2,10,11];Zou, Yunzeng[3,4];Ye, Dan[1,2,12]

机构：[1]Fudan Univ, Key Lab Metab & Mol Med, Minist Educ, Shanghai, Peoples R China;[2]Fudan Univ, Mol & Cell Biol Lab, Key Lab Med Epigenet & Metab, Inst Biomed Sci,Shanghai Med Coll, Shanghai, Peoples R China;[3]Fudan Univ, Shanghai Inst Cardiovasc Dis, Zhongshan Hosp, Shanghai, Peoples R China;[4]Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China;[5]Fudan Univ, Shanghai Med Coll, Dept Thorac Surg, Shanghai, Peoples R China;[6]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China;[7]Waters Corp Shanghai Sci & Technol Co Ltd, Shanghai, Peoples R China;[8]East China Univ Sci & Technol, Sch Pharm, Shanghai, Peoples R China;[9]Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC USA;[10]Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA;[11]Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA;[12]Fudan Univ, Dept Gen Surg, Huashan Hosp, Shanghai, Peoples R China

年份：2019

卷号：14

期号：2

外文期刊名：PLOS ONE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000458761300058)】；

基金：This work was supported by the National Key R&D Program of China (http://www.most.gov.cn/) (no. 2016YFA0501800 to DY), the National Natural Science Foundation of China grants (http://www.nsfc.gov.cn/english/site_1/index.html) (no. 31871431 and no. 81522033 to DY) and the Shanghai Committee of Science and Technology, China (http:/www.stcsm.gov.cn/english/) (no.16JC1404000 to DY). This work was also supported by Waters corporation Shanghai Science & Technology Co Ltd (http./www.waters.com/waters/home.htm?locale=zh_CN) (salaries to XXW and HW). The funder provided support in the form of salaries for authors (XXW and HW), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. The other funders in our study also had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

摘要：Sirtuin 5 (SIRT5) is a member of the NAW-dependent sirtuin family of protein deacylase that catalyzes removal of post-translational modifications, such as succinylation, malonylation, and glutarylation on lysine residues. In light of the SIRT5's roles in regulating mitochondrion function, we show here that SIRT5 deficiency leads to suppression of mitochondrial NADH oxidation and inhibition of ATP synthase activity. As a result, SIRT5 deficiency decreases mitochondrial ATP production, increases AMP/ATP ratio, and subsequently activates AMP-activated protein kinase (AMPK) in cultured cells and mouse hearts under energy stress conditions. Moreover, Sirt5 knockout attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy and cardiac dysfunction in mice, which is associated with decreased ATP level, increased AMP/ATP ratio and enhanced AMPK activation. Our study thus uncovers an important role of SIRT5 in regulating cellular energy metabolism and AMPK activation in response to energy stress.