Both Thioredoxin 2 and Glutaredoxin 2 Contribute to the Reduction of the Mitochondrial 2-Cys Peroxiredoxin Prx3

作者：Eva-Maria Hanschmann, Maria Elisabet Lönn, Lena Dorothee Schütte, Maria Funke, José R. Godoy, Susanne Eitner, Christoph Hudemann, Christopher Horst Lillig · 发表于：Journal of Biological Chemistry · 年份：2010 · DOI：10.1074/jbc.m110.185827 · 被引用次数：109 · 研究领域：Redox biology and oxidative stress、Heat shock proteins research、Glutathione Transferases and Polymorphisms

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 μmol·liter(-1); V(max), 1.2 μmol·(mg·min)(-1)) similar to Trx2 (K(m), 11.2 μmol·liter(-1); V(max), 1.1 μmol·(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.