Both thioredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3

J Biol Chem. 2010 Dec 24;285(52):40699-705. doi: 10.1074/jbc.M110.185827. Epub 2010 Oct 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Gene Silencing
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism*
  • HeLa Cells
  • Humans
  • Mice
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Organ Specificity / physiology
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • Peroxiredoxin III
  • Peroxiredoxins / genetics
  • Peroxiredoxins / metabolism*
  • Protein Multimerization / physiology
  • Rats
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*


  • Glutaredoxins
  • Mitochondrial Proteins
  • Prdx3 protein, mouse
  • TXN2 protein, human
  • Txn2 protein, rat
  • Thioredoxins
  • PRDX3 protein, human
  • Peroxiredoxin III
  • Peroxiredoxins