Both Thioredoxin 2 and Glutaredoxin 2 Contribute to the Reduction of the Mitochondrial 2-Cys Peroxiredoxin Prx3
Both Thioredoxin 2 and Glutaredoxin 2 Contribute to the Reduction of the Mitochondrial 2-Cys Peroxiredoxin Prx3
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DOI：
10.1074/jbc.m110.185827
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发表时间：
2010-12-24
影响因子：
4.8
通讯作者：
Lillig, Christopher Horst
中科院分区：
文献类型：
--
作者：
Hanschmann, Eva-Maria;Loenn, Maria Elisabet;Lillig, Christopher Horst
来自硫氧还蛋白家族的蛋白质在氧化还原信号传导和细胞对氧化应激的反应中是至关重要的作用者。氧自由基的主要细胞内来源是线粒体中呼吸链的组分。在这里，我们表明，线粒体2-半胱氨酸过氧化物氧还蛋白（Prx 3）不仅是硫氧还蛋白2（Trx 2）的底物，但也可以通过二巯基反应机制被谷氧还蛋白2（Grx 2）还原。Grx 2还原Prx 3，表现出催化常数（K-m，23.8 μ mol. L（-1）; V-max，1.2 μ mol. L（-1））。（mg.min）（-1））类似于Trx 2（K-m，11.2 μ mol. L（-1）; V-max，1.1 μ mol.（mg.min）（-1））。非典型2-Cys Prx 5的催化二硫键的还原仅限于Trx系统。使用特异性siRNA沉默HeLa细胞中Trx 2或Grx 2的表达并没有改变通过特异性2-Cys Prx氧化还原印迹检测到的Prx 3的单体：二聚体比率。只有两种蛋白表达的组合沉默导致氧化蛋白的积累。我们进一步证明了Prx 3在不同小鼠组织中的分布与Trx 2或Grx 2的分布有关。这些结果引入Grx 2作为Prx 3的新型电子供体，为关键的细胞氧化还原信号传导机制提供了进一步的见解。
The proteins from the thioredoxin family are crucial actors in redox signaling and the cellular response to oxidative stress. The major intracellular source for oxygen radicals are the components of the respiratory chain in mitochondria. Here, we show that the mitochondrial 2-Cys peroxiredoxin (Prx3) is not only substrate for thioredoxin 2 (Trx2), but can also be reduced by glutaredoxin 2 (Grx2) via the dithiol reaction mechanism. Grx2 reduces Prx3 exhibiting catalytic constants (K-m, 23.8 mu mol.liter(-1); V-max, 1.2 mu mol.(mg.min)(-1)) similar to Trx2 (K-m, 11.2 mu mol.liter(-1); V-max, 1.1 mu mol.(mg.min)(-1)). The reduction of the catalytic disulfide of the atypical 2-Cys Prx5 is limited to the Trx system. Silencing the expression of either Trx2 or Grx2 in HeLa cells using specific siRNAs did not change the monomer: dimer ratio of Prx3 detected by a specific 2-Cys Prx redox blot. Only combined silencing of the expression of both proteins led to an accumulation of oxidized protein. We further demonstrate that the distribution of Prx3 in different mouse tissues is either linked to the distribution of Trx2 or Grx2. These results introduce Grx2 as a novel electron donor for Prx3, providing further insights into pivotal cellular redox signaling mechanisms.