Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.
Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.
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DOI：
10.1371/journal.pone.0106028
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Goetzman ES
中科院分区：
文献类型：
--
作者：
de Moura MB;Uppala R;Zhang Y;Van Houten B;Goetzman ES
SIRT3、SIRT4 和 SIRT5 是线粒体脱酰酶，影响能量代谢和线粒体功能的多个方面。 SIRT3 激活多种线粒体酶，SIRT4 抑制其靶标，而 SIRT5 已被证明既激活又抑制线粒体酶。为了深入了解线粒体 Sirtuins 在控制线粒体能量代谢中的相对作用，直接比较了 SIRT3、SIRT4 和 SIRT5 过表达的 HEK293 细胞。当在标准细胞培养条件（25 mM 葡萄糖）下生长时，所有三种去乙酰化酶均诱导线粒体呼吸、糖酵解和葡萄糖氧化增加，但生长速率或稳态 ATP 浓度没有变化。寡霉素存在下的耗氧量证明，质子泄漏增加似乎可以解释基础氧利用增加的大部分原因。所有sirtuin 过表达细胞中，5 mM 葡萄糖中的生长使基础耗氧量、质子泄漏和糖酵解的升高正常化。虽然上述效应对于所有三种线粒体 Sirtuins 来说都是常见的，但注意到 SIRT3、SIRT4 和 SIRT5 表达细胞之间的一些差异。只有 SIRT3 过表达影响脂肪酸代谢，只有 SIRT4 过表达改变超氧化物水平和线粒体膜电位。我们得出的结论是，所有三种线粒体去乙酰化酶都可以促进线粒体呼吸和细胞代谢的增加。 SIRT3、SIRT4 和 SIRT5 似乎通过诱导糖酵解和呼吸协调增加来响应过量葡萄糖，并通过质子泄漏消散多余的能量。
SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose) all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.
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影响因子：
16
作者：
Laurent, Gaelle;German, Natalie J.;Saha, Asish K.;de Boer, Vincent C. J.;Davies, Michael;Koves, Timothy R.;Dephoure, Noah;Fischer, Frank;Boanca, Gina;Vaitheesvaran, Bhavapriya;Lovitch, Scott B.;Sharpe, Arlene H.;Kurland, Irwin J.;Steegborn, Clemens;Gygi, Steven P.;Muoio, Deborah M.;Ruderman, Neil B.;Haigis, Marcia C.
通讯作者：
Haigis, Marcia C.
肿瘤抑制因子 SIRT3 脱乙酰并激活锰超氧化物歧化酶清除 ROS
影响因子：
7.7
作者：
Chen, Yaohui;Zhang, Jinye;Lin, Yan;Lei, Qunying;Guan, Kun-Liang;Zhao, Shimin;Xiong, Yue
通讯作者：
Xiong, Yue
影响因子：
6.4
作者：
Anderson KA;Hirschey MD
通讯作者：
Hirschey MD
影响因子：
6.4
作者：
Jastroch M;Divakaruni AS;Mookerjee S;Treberg JR;Brand MD
通讯作者：
Brand MD
DOI：
10.18632/aging.100616
发表时间：
2013-11
期刊：
Aging
影响因子：
--
作者：
Ho L;Titus AS;Banerjee KK;George S;Lin W;Deota S;Saha AK;Nakamura K;Gut P;Verdin E;Kolthur-Seetharam U
通讯作者：
Kolthur-Seetharam U