Search

Peroxiredoxin 5 (PRDX5) is a thioredoxin peroxidase able to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. In human, PRDX5 was reported to be localized in the cytosol, the mitochondria, the peroxisomes and the nucleus. Mitochondrial localization results from the presence of an N-terminal mitochondrial targeting sequence (MTS). Here, we examined the conservation of mitochondrial localization of PRDX5 in animal species. We found that PRDX5 MTS is present and functional in the annelid lugworm Arenicola marina. Surprisingly, although mitochondrial targeting is well conserved among animals, PRDX5 is missing in mitochondria of domestic pig. Thus, it appears that mitochondrial targeting of PRDX5 may have been lost throughout evolution in animal species, including pig, with unknown functional consequences.

Peroxiredoxin 5 (PRDX5) was the last member to be identified among the six mammalian peroxiredoxins. It is also the unique atypical 2-Cys peroxiredoxin in mammals. Like the other five members, PRDX5 is widely expressed in tissues but differs by its surprisingly large subcellular distribution. In human cells, it has been shown that PRDX5 can be addressed to mitochondria, peroxisomes, the cytosol, and the nucleus. PRDX5 is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite with high rate constants in the 10(6) to 10(7) M(-1)s(-1) range, whereas its reaction with hydrogen peroxide is more modest, in the 10(5) M(-1)s(-1) range. PRDX5 crystal structures confirmed the proposed enzymatic mechanisms based on biochemical data but revealed also some specific unexpected structural features. So far, PRDX5 has been viewed mainly as a cytoprotective antioxidant enzyme acting against endogenous or exogenous peroxide attacks rather than as a redox sensor. Accordingly, overexpression of the enzyme in different subcellular compartments protects cells against death caused by nitro-oxidative stresses, whereas gene silencing makes them more vulnerable. Thus, more than 10 years after its molecular cloning, mammalian PRDX5 appears to be a unique peroxiredoxin exhibiting specific functional and structural features.

Peroxiredoxins compose a superfamily of peroxidases ubiquitously found throughout evolution in prokaryotes, archaea and eukaryotes. These enzymes contain a conserved catalytic peroxidatic cysteine (Cp) in the N-terminal region of the protein. The residues surrounding Cp and the catalytic site appear also to be well conserved. Peroxiredoxins can be classified either into three subfamilies according to their catalytic mechanism or into five subfamilies according to sequence homology. Notably, the number of peroxiredoxin genes increased during evolution. In eukaryotes, the higher number of genes coding for peroxiredoxin family members is due to the existence of different isoforms targeted to different subcellular compartments but is probably due also to the acquisition of new functions. Indeed, it has been postulated that the antioxidant protective role of peroxiredoxins, which is particularly critical in prokaryotes, in yeasts and in parasitic eukaryotes, may have evolved to a modulatory role in hydrogen peroxide signaling in plants and animals.

Peroxiredoxins compose a superfamily of peroxidases ubiquitously found throughout evolution in prokaryotes, archaea and eukaryotes. These enzymes contain a conserved catalytic peroxidatic cysteine (Cp) in the N-terminal region of the protein. The residues surrounding Cp and the catalytic site appear also to be well conserved. Peroxiredoxins can be classified either into three subfamilies according to their catalytic mechanism or into five subfamilies according to sequence homology. Notably, the number of peroxiredoxin genes increased during evolution. In eukaryotes, the higher number of genes coding for peroxiredoxin family members is due to the existence of different isoforms targeted to different subcellular compartments but is probably due also to the acquisition of new functions. Indeed, it has been postulated that the antioxidant protective role of peroxiredoxins, which is particularly critical in prokaryotes, in yeasts and in parasitic eukaryotes, may have evolved to a modulatory role in hydrogen peroxide signaling in plants and animals.

Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. Its role as antioxidant enzyme has been previously supported in different pathological situations. In this study, we determined the complete human PRDX5 genomic organization and isolated the 5'-flanking region of the gene. Human PRDX5 gene is composed of six exons and five introns similarly to other chordate PRDX5 genes. Several single nucleotide polymorphisms were identified. Six out of them have amino acid substitutions in protein-coding region. Analysis of the 5'-flanking region of human PRDX5 revealed the presence of a TATA-less promoter containing a canonical CpG island and several putative response elements for transcription factors. To analyze the regulatory mechanisms controlling human PRDX5 expression, we characterized the 5'-flanking region by cloning various segments of this region in front of a luciferase reporter sequence. Transfection in HepG2 cells indicate that the 5'-flanking region contains regulatory elements for constitutive expression of human PRDX5. Multiple transcription start sites were also identified by 5'-RACE-PCR in human liver. Moreover, although no corresponding proteins were reported, we present new alternative splicing variants encoded specifically by human PRDX5 gene. The characterization of human PRDX5 gene revealed the complexity of its regulation and a high variability of sequences that might be associated with pathological situations.