Mild metabolic perturbations alter succinylation of mitochondrial proteins.
Mild metabolic perturbations alter succinylation of mitochondrial proteins.
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DOI：
10.1002/jnr.24103
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发表时间：
2017-11
影响因子：
4.2
通讯作者：
Gibson GE
中科院分区：
文献类型：
--
作者：
Chen H;Xu H;Potash S;Starkov A;Belousov VV;Bilan DS;Denton TT;Gibson GE
蛋白质的琥珀酰化广泛存在，改变分子的电荷和大小，并可以改变它们的功能。例如，肝线粒体蛋白具有1190个独特的琥珀酰化位点，代表多种代谢途径。琥珀酰化对NAD+依赖性脱琥珀酰酶SIRT 5的增加和减少都敏感。虽然琥珀酰化的琥珀酰基来源于代谢，但代谢的系统性变化对线粒体琥珀酰化的影响尚不清楚。线粒体蛋白琥珀酰化的变化后，代谢的变化进行了比较，线粒体的氧化还原状态估计线粒体NAD+/NADH的比例，使用荧光探针。减少糖酵解和/或谷胱甘肽耗尽（碘乙酸; 2-脱氧葡萄糖），三羧酸循环活性（琥珀酰膦酸羧乙酯）和电子传递（抗霉素）或ATP合酶（寡霉素）的损害，而氧化磷酸化解偶联剂（羰基氰间氯苯肼或triphostin）增加NAD+/NADH的比例降低。所有条件都降低了琥珀酰化作用。相反，将氧从20%减少到2.4%增加了琥珀酰化。结果表明，琥珀酰化随代谢状态而变化，与线粒体NAD+/NADH比值无关，并可能有助于协调对代谢挑战的反应。
Succinylation of proteins is wide-spread, modifies both the charge and size of the molecules and can alter their function. For example, liver mitochondrial proteins have 1190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD+ dependent de-succinylase, SIRT5. Although the succinyl group for succinylation is derived from metabolism, the effects of systematic variation of metabolism on mitochondrial succinylation are not known. Changes in succinylation of mitochondrial proteins following variations in metabolism were compared to mitochondrial redox state as estimated by the mitochondrial NAD+/NADH ratio using fluorescent probes. The ratio was decreased by reduced glycolysis and/or glutathione depletion (iodo-acetic acid; 2-deoxyglucose), depressed tricarboxylic acid cycle activity (carboxyethyl ester of succinyl phosphonate) and impairment of electron transport (antimycin) or ATP synthase (oligomycin), while uncouplers of oxidative phosphorylation (carbonyl cyanide m-chlorophenyl hydrazine or triphostin) increased the NAD+/NADH ratio. All of the conditions decreased succinylation. In contrast, reducing the oxygen from 20% to 2.4% increased succinylation. The results demonstrate that succinylation varies with metabolic states, is not correlated to the mitochondrial NAD+/NADH ratio and may help co-ordinate the response to metabolic challenge.
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影响因子：
3
作者：
Bilan, Dmitry S.;Matlashov, Mikhail E.;Gorokhovatsky, Andrey Yu.;Schultz, Carsten;Enikolopov, Grigori;Belousov, Vsevolod V.
通讯作者：
Belousov, Vsevolod V.
影响因子：
3.7
作者：
de Moura MB;Uppala R;Zhang Y;Van Houten B;Goetzman ES
通讯作者：
Goetzman ES
影响因子：
4.8
作者：
Li, NY;Ragheb, K;Robinson, JP
通讯作者：
Robinson, JP
影响因子：
3.3
作者：
Kim, A. Young;Jeong, Kyeong-Hoon;Baik, Eun Joo
通讯作者：
Baik, Eun Joo
DOI：
10.3389/neuro.14.001.2009
发表时间：
2009-01-01
期刊：
Frontiers in neuroenergetics
影响因子：
--
作者：
Schmidt, Maike M;Dringen, Ralf
通讯作者：
Dringen, Ralf