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

• Published in: EMBO reports Vol. 19; no. 5
• Main Authors: Chen, Xiu‐Fei, Tian, Meng‐Xin, Sun, Ren‐Qiang, Zhang, Meng‐Li, Zhou, Li‐Sha, Jin, Lei, Chen, Lei‐Lei, Zhou, Wen‐Jie, Duan, Kun‐Long, Chen, Yu‐Jia, Gao, Chao, Cheng, Zhou‐Li, Wang, Fang, Zhang, Jin‐Ye, Sun, Yi‐Ping, Yu, Hong‐Xiu, Zhao, Yu‐Zheng, Yang, Yi, Liu, Wei‐Ren, Shi, Ying‐Hong, Xiong, Yue, Guan, Kun‐Liang, Ye, Dan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Springer Nature B.V; John Wiley and Sons Inc
• Subjects: ACOX1; Acyl-CoA Oxidase - antagonists & inhibitors; Acyl-CoA Oxidase - genetics; Acyl-CoA Oxidase - metabolism; Animals; Carcinoma, Hepatocellular - metabolism; Clonal deletion; Damage prevention; Deoxyribonucleic acid; Dimers; DNA; DNA Damage; Down-Regulation; EMBO03; EMBO29; EMBO31; Female; Gene Knockdown Techniques; HEK293 Cells; HeLa Cells; Hep G2 Cells; Hepatocellular carcinoma; Homeostasis; Humans; Hydrogen Peroxide; Liver; Liver cancer; Liver Neoplasms - metabolism; Male; Metabolism; Mice; Mice, Knockout; Middle Aged; Oxidation; Oxidation-Reduction; Oxidative Stress; Peroxisomes; Peroxisomes - chemistry; Prognosis; Reactive oxygen species; SIRT5; Sirtuins - genetics; Sirtuins - metabolism; succinylation; SIRT5; liver cancer; succinylation; ACOX1; oxidative stress

Peroxisomes account for ~35% of total H 2 O 2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer of H 2 O 2 . ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here,...