| First Author | Tao R | Year | 2010 |
| Journal | Mol Cell | Volume | 40 |
| Issue | 6 | Pages | 893-904 |
| PubMed ID | 21172655 | Mgi Jnum | J:168095 |
| Mgi Id | MGI:4881871 | Doi | 10.1016/j.molcel.2010.12.013 |
| Citation | Tao R, et al. (2010) Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40(6):893-904 |
| abstractText | Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development. MnSOD contains a nutrient- and ionizing radiation (IR)-dependent reversible acetyl-lysine that is hyperacetylated in Sirt3/ livers at 3 months of age. Livers of Sirt3/ mice exhibit decreased MnSOD activity, but not immunoreactive protein, relative to wild-type livers. Reintroduction of wild-type but not deacetylation null Sirt3 into Sirt3/ MEFs deacetylated lysine and restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity when expressed in MnSOD/ MEFs, suggesting acetylation directly regulates function. Furthermore, infection of Sirt3/ MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide. Finally, IR was unable to induce MnSOD deacetylation or activity in Sirt3/ livers, and these irradiated livers displayed significant IR-induced cell damage and microvacuolization in their hepatocytes. |
