title: Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS.
abstract: Mitochondria manganese superoxide dismutase (SOD2) is an important antioxidant enzyme, deficiency of which is associated with various human diseases. The known primary regulation of SOD2 is through transcriptional activation. Here, we report that SOD2 is acetylated at Lys 68 and that this acetylation decreases SOD2 activity. Mitochondrial deacetylase SIRT3 binds to, deacetylates and activates SOD2. Increase of reactive oxygen species (ROS) levels stimulates SIRT3 transcription, leading to SOD2 deacetylation and activation. SOD2-mediated ROS reduction is synergistically increased by SIRT3 co-expression, but is cancelled by SIRT3 depletion. These results reveal a new post-translational regulation of SOD2 by means of acetylation and SIRT3-dependent deacetylation in response to oxidative stress.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Science, Novartis-Fudan Joint Research Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Chen
authors.forename: Jinye
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Qunying
authors.initials: Q
authors.lastname: Lei
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D004789:Enzyme Activation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016415:Sequence Alignment; D056566:Sirtuin 3 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C466093:SIRT3 protein, human; D056566:Sirtuin 3