title: SIRT5 desuccinylates and activates SOD1 to eliminate ROS.
abstract: Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells.
authors.affiliation: Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Lin
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Xu
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ruan
authors.forename: Fa-Bing
authors.initials: FB
authors.lastname: Liu
authors.forename: Wang
authors.initials: W
authors.lastname: Jin
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Huang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013386:Succinates; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C508544:SIRT5 protein, human; D037761:Sirtuins; D008239:Lysine
keywords: Antioxidation; Cell growth; ROS; SIRT5; Succinylation