Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity.
Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity.
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DOI：
10.1016/j.freeradbiomed.2012.06.020
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发表时间：
2012-08-15
影响因子：
7.4
通讯作者：
Gius, David
中科院分区：
文献类型：
--
作者：
Zhu, Yueming;Park, Seong-Hoon;Ozden, Ozkan;Kim, Hyun-Seok;Jiang, Haiyan;Vassilopoulos, Athanassios;Spitz, Douglas R.;Gius, David
关键词：
线粒体氧化代谢是 ATP 产生的主要场所，也是活性氧 (ROS) 的重要来源，可对关键生物分子造成损害。众所周知，应激反应蛋白靶向清除ROS的线粒体酶，以维持线粒体功能的保真度。锰超氧化物歧化酶 (MnSOD) 是一种主要的线粒体 ROS 清除酶，1983 年 Irwin Fridovich 提出了一种优雅的化学机制/模型，通过乙酰化指导 MnSOD 酶活性。他将其命名为“静电斥力模型”。然而，决定乙酰化如何指导活性的生化和遗传机制以及对多层转录和翻译后 MnSOD 调节的进化保守性需求背后的原因仍然未知。在这方面，我们和其他人已经证明，MnSOD 至少部分是通过线粒体 Sirtuin Sirt3 催化的反应中特定保守赖氨酸的脱乙酰化来调节的。我们推测赖氨酸乙酰化通过静电排斥机制对 MnSOD 活性的调节是维持线粒体稳态所必需的 MnSOD 调节的保守且关键的方面。
Mitochondrial oxidative metabolism is the major site of ATP production as well as a significant source of reactive oxygen species (ROS) that can cause damage to critical biomolecules. It is well known that mitochondrial enzymes that scavenge ROS are targeted by stress responsive proteins to maintain the fidelity of mitochondrial function. Manganese superoxide dismutase (MnSOD) is a primary mitochondrial ROS scavenging enzyme, and in 1983 Irwin Fridovich proposed an elegant chemical mechanism/model whereby acetylation directs MnSOD enzymatic activity. He christened it the “electrostatic repulsion model”. However, the biochemical and genetic mechanism(s) determining how acetylation directs activity and the reasons behind the evolutionarily conserved need for several layers of transcriptional and post-translational MnSOD regulation remain unknown. In this regard, we and others have shown that MnSOD is regulated, at least in part, by the deacetylation of specific conserved lysines in a reaction catalyzed by the mitochondrial sirtuin, Sirt3. We speculate that the regulation of MnSOD activity by lysine acetylation via an electrostatic repulsion mechanism is a conserved and critical aspect of MnSOD regulation necessary to maintain mitochondrial homeostasis.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
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：
4.8
作者：
Judge, S;Jang, YM;Leeuwenburgh, C
通讯作者：
Leeuwenburgh, C
影响因子：
3.1
作者：
Gius, D;Mattson, D;Spitz, DR
通讯作者：
Spitz, DR
DOI：
10.1101/sqb.2000.65.297
发表时间：
2000-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Imai, S;Johnson, FB;Guarente, L
通讯作者：
Guarente, L