Mitochondria of Saccharomyces cerevisiae contain one-conserved cysteine type peroxiredoxin with thioredoxin peroxidase activity

Peroxiredoxins are ubiquitously expressed proteins that reduce hydroperoxid es using disulfur-reducing compounds as electron donors. Peroxiredoxins (Pr xs) have been classified in two groups dependent on the presence of either one (l-Cys Prx) or two (a-Cys Prx) conserved cysteine residues. Moreover, 8 -Cys Prxs, also named thioredoxin peroxidases, have peroxide reductase acti vity with the use of thioredoxin as biological electron donor. However, the biological reducing agent for the l-Cys Prx has not yet been identified. W e report here the characterization of a l-Cys Prx from yeast Saccharomyces cerevisiae that we have named Prx1p. Prx1p is located in mitochondria, and it is overexpressed when cells use the respiratory pathway, as well as in r esponse to oxidative stress conditions. We show also that Prx1p has peroxid e reductase activity in vitro using the yeast mitochondrial thioredoxin sys tem as electron donor. In addition, a mutated form of Prx1p containing the absolutely conserved cysteine as the only cysteine residue also shows thior edoxin-dependent peroxide reductase activity. This is the first example of 1-Cys Prx that has thioredoxin peroxidase activity. Finally, exposure of nu ll Prxlp mutant cells to oxidant conditions reveals an important role of th e mitochondrial 1-Cys Prx in protection against oxidative stress.