Piecing Together How Peroxiredoxins Maintain Genomic Stability

Abstract

Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (Saccharomyces cerevisiae) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species.

Characteristics of the Equine Placenta at First Trimester

“…In addition, the most enriched ontology in allantois fluid is the peroxidoxin activity. Peroxidoxin in an antioxidant enzyme related to genome stability (West et al, 2018). Then, we can hypothesize that the high metabolic allantois epithelium could produce peroxidoxin to inhibit possible oxidants eliminated in the allantois fluid by fetal metabolism.…”

The Peroxiredoxin Asp f3 Acts as Redox Sensor in Aspergillus fumigatus

“…This observation is in line with earlier results for Saccharomyces cerevisiae which demonstrated that the yeast was still viable despite a deletion of all five peroxiredoxin genes and that single mutants grew like the wild type in aerobic conditions [ 36 ]. Interestingly, the authors also showed that the Asp f3 orthologue in yeast, Tsa1p, secured long-term genomic stability by preventing mutations [ 37 , 38 ]. Such a protective function may well be conserved in A. fumigatus but would most likely not explain the avirulent phenotype of the Δ asp f3 strain in the aspergillosis animal model.…”

AAED1 (AhpC/TSA antioxidant enzyme domain containing 1)

“…A peroxidatic cysteine reduces the peroxide to water. Thioredoxin system reduce peroxiredoxins restoring to them their catalytically active form (West et al, 2018).…”