Sirt3 Mediated Deacetylation of Evolutionarily Conserved Lysine 122 Regulates MnSOD Activity in Response to Stress
Yazarlar (13)
Randa Tao
Türkiye
Mitchell C Coleman
Türkiye
J Daniel Pennington
Türkiye
Seong-Hoon Park
Türkiye
Haiyan Jiang
Türkiye
Hyun-Seok Kim
Türkiye
Charles Robb Flynn
Türkiye
Salisha Hill
Türkiye
Mcdonald W Hayes
Türkiye
Alicia K Olivier
Türkiye
Douglas R Spitz
Türkiye
David Gius
Türkiye
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
|
||
| Dergi Adı | MOLECULAR CELL | ||
| Dergi ISSN | 1097-2765 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI | ||
| Makale Dili | İngilizce | Basım Tarihi | 12-2010 |
| Cilt / Sayı / Sayfa | 40 / 6 / 893–904 | DOI | 10.1016/j.molcel.2010.12.013 |
| Makale Linki | http://linkinghub.elsevier.com/retrieve/pii/S109727651000969X | ||
| Özet |
| 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. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 772 |