SIRT3 Deacetylates Isocitrate Dehydrogenase 2 (IDH2) and Regulates Mitochondrial Redox Status
نویسندگان
چکیده
From Department of Biomolecular Chemistry and the Wisconsin Institute Discovery, University of Wisconsin-‐Madison, Madison, Wisconsin 53715 Running head: Sirt3 Deacetylates IDH2 and regulates redox status Address correspondence to: John M. Denu Ph.D., 2140 Wisconsin Institute of Discovery, 330 N Orchard Street, Madison, WI 53715. Fax: 608-‐316-‐4602; E-‐mail: [email protected] Background: NAD-dependent deacetylase SIRT3 is essential for the prevention of agerelated hearing loss during caloric restriction. Results: Oxidative stress resistance by SIRT3 was mediated through IDH2. SIRT3 deacetylates IDH2 at lysine 413 and stimulates activity by as much as 44-fold. Conclusion: Increased SIRT3 expression protects cells from oxidative stress through IDH2 activation. Significance: Our results provide the mechanism by which SIRT3 regulates IDH2.
منابع مشابه
Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction
Caloric restriction (CR) extends the life span and health span of a variety of species and slows the progression of age-related hearing loss (AHL), a common age-related disorder associated with oxidative stress. Here, we report that CR reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type mice but fails to modify these phenotypes in mice lacking the mitochondrial deacet...
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