The curious case of peroxiredoxin-5: what its absence in aves can tell us and how it can be used

Abstract

BackgroundPeroxiredoxins are ubiquitous thiol-dependent peroxidases that represent a major antioxidant defense in both prokaryotic cells and eukaryotic organisms. Among the six vertebrate peroxiredoxin isoforms, peroxiredoxin-5 (PRDX5) appears to be a particular peroxiredoxin, displaying a different catalytic mechanism, as well as a wider substrate specificity and subcellular distribution. In addition, several evolutionary peculiarities, such as loss of subcellular targeting in certain species, have been reported for this enzyme.ResultsWestern blotting analyses of 2-cys PRDXs (PRDX1–5) failed to identify the PRDX5 isoform in chicken tissue homogenates. Thereafter, via in silico analysis of PRDX5 orthologs, we went on to show that the PRDX5 gene is conserved in all branches of the amniotes clade, with the exception of aves. Further investigation of bird genomic sequences and expressed tag sequences confirmed the disappearance of the gene, though TRMT112, a gene located closely to the 5′ extremity of the PRDX5 gene, is conserved. Finally, using in ovo electroporation to overexpress the long and short forms of human PRDX5, we showed that, though the gene is lost in birds, subcellular targeting of human PRDX5 is conserved in the chick.ConclusionsFurther adding to the distinctiveness of this enzyme, this study reports converging evidence supporting loss of PRDX5 in aves. In-depth analysis revealed that this absence is proper to birds as PRDX5 appears to be conserved in non-avian amniotes. Finally, taking advantage of the in ovo electroporation technique, we validate the subcellular targeting of human PRDX5 in the chick embryo and bring forward this gain-of-function model as a potent way to study PRDX5 functions in vivo.

Molecular Drivers of Lymphocyte Organization in Vertebrate Mucosal Surfaces: Revisiting the TNF Superfamily Hypothesis

“…The loss of lymphotoxins in birds is not a rare event. Birds have the unique ability to compensate for losses in numerous immune genes/loci, including the Ig kappa L chain, peroxiredoxin, and other TNFSF members (15,(85)(86)(87). Thus, in agreement with previously published studies (32,54), we found that bird genomes do not contain TNFSF1, TNFSF3, or TNFRSF3.…”

PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40

“…However, we cannot eliminate the possibility that ROSinduced DNA damage in mitochondrial DNA causes cell death in PRDX1-depleted cells. Among the 6 PRDX family genes reported in vertebrates, PRDX5, which contains the mitochondrial targeting sequence, is absent in the aves genome [32,33]. Aves PRDX1 localizes to the cytosol but may have an unknown role in the maintenance of mitochondrial ROS for proper cell growth.…”

Discovery of Antitumor Active Peptides Derived from Peroxiredoxin 5

“…Indeed, two alternative translation initiation sites lead to two forms of PRDX5: a long form (L‐PRDX5), which is addressed to mitochondria with the mitochondrial targeting sequence (MTS), and a short form (S‐PRDX5), which is located in the cytosol, nucleus and peroxisomes [11] . MTS in L‐PRDX5 is cleaved after mitochondrial import, producing a mature mitochondrial PRDX5 identical to S‐PRDX5 [12] . Therefore, in our previous investigation and this study, S‐PRDX5 was selected as the target protein for further research.…”