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Sirt3‐dependent deacetylation of COX‐1 counteracts oxidative stress‐induced cell apoptosis
Author(s) -
Tu LongFang,
Cao LingFang,
Zhang YueHong,
Guo YuLin,
Zhou YangFan,
Lu WeiQi,
Zhang TianZe,
Zhang Tao,
Zhang GaoXiao,
Kurihara Hiroshi,
Li YiFang,
He RongRong
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900708r
Subject(s) - sirt3 , oxidative stress , acetylation , apoptosis , programmed cell death , chemistry , mitochondrion , microbiology and biotechnology , sirtuin , oxidative phosphorylation , biochemistry , biology , gene
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. FASEB J. 33, 14118‐14128 (2019). www.fasebj.org