Sirt3‐dependent deacetylation of COX‐1 counteracts oxidative stress‐induced cell apoptosis

Autor: Tao Zhang, Yue-Hong Zhang, Gao-Xiao Zhang, Yang-Fan Zhou, Long-Fang Tu, Hiroshi Kurihara, Yu-Lin Guo, Wei-Qi Lu, Ling-Fang Cao, Rong-Rong He, Yi-Fang Li, Tian-Ze Zhang
Rok vydání: 2019
Předmět:
Zdroj: The FASEB Journal. 33:14118-14128
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201900708r
Popis: The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.
Databáze: OpenAIRE
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