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SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer 期刊论文

编号：

e4f91e86-53c9-4c77-9162-549333a917ce
作者：

Chen, XiuFei^[1,2,3];Tian, MengXin^[4,5]Sun, RenQiang^[1,2,3];Zhang, MengLi^[1,2,3];Zhou, LiSha^[1,2,3];Jin, Lei^[4,5];Chen, LeiLei^[1,2,3];Zhou, WenJie^[1,2,3];Duan, KunLong^[1,2,3];Chen, YuJia^[1,2,3];Gao, Chao^[1,2,3];Cheng, ZhouLi^[1,2,3];Wang, Fang^[1,2,3];Zhang, JinYe^[1,2,3];Sun, YiPing^[1,2,3];Yu, HongXiu(余红秀)^[1,2,3]Zhao, YuZheng^[6];Yang, Yi^[6];Liu, WeiRen^[4,5];Shi, YingHong(史颖弘)^[4,5]Xiong, Yue^[1,2,3,7];Guan, KunLiang^[1,2,3,8,9];Ye, Dan(叶丹)*^[1,2,3,10]
语种：

English
期刊：

EMBO REPORTS ISSN：1469-221X 2018 年 19 卷 5 期 ; MAY
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关键词：

ACOX1 liver cancer oxidative stress SIRT5 succinylation
摘要：

Peroxisomes account for similar to 35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl-CoA oxidase 1) is the first and rate-limiting enzyme in fatty acid beta-oxidation and a major producer of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5-mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome-induced oxidative stress, in liver protection, and in suppressing HCC development.
推荐引用方式
GB/T 7714：

Chen Xiu-Fei,Tian Meng-Xin,Sun Ren-Qiang, et al. SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer [J].EMBO REPORTS,2018,19(5).
APA：

Chen Xiu-Fei,Tian Meng-Xin,Sun Ren-Qiang,Zhang Meng-Li,&Ye Dan.(2018).SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer .EMBO REPORTS,19(5).
MLA：

Chen Xiu-Fei, et al. "SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer" .EMBO REPORTS 19,5(2018).
入库时间：

2019/5/28 18:31:38
更新时间：

2019/5/28 18:31:38

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