Peroxiredoxins (Prdxs) sense and assess peroxide levels, and signal through protein interactions. Understanding the role of the multiple structural and post-translational modification (PTM) layers that tunes the peroxiredoxin specificities is still a challenge. In this review, we give a tabulated overview on what is known about human and bacterial peroxiredoxins with a focus on structure, PTMs, and protein-protein interactions. Armed with numerous cellular and atomic level experimental techniques, we look at the future and ask ourselves what is still needed to give us a clearer view on the cellular operating power of Prdxs in both stress and non-stress conditions.

Members of the DJ-1 protein family are multifunctional enzymes whose loss increases the susceptibility of the cell to oxidative stress. However, little is known about the function of the plant DJ-1 homologs. Therefore, we analyzed the effect of oxidation on the structure and function of chloroplastic AtDJ-1B and studied the phenotype of T-DNA lines lacking the protein. In vitro oxidation of AtDJ-1B with H₂O₂ lowers its glyoxalase activity, but has no effect on its holdase chaperone function. Remarkably, upon oxidation, the thermostability of AtDJ-1B increases with no significant alteration of the overall secondary structure. Moreover, we found that AtDJ-1B transcript levels are invariable, and loss of AtDJ-1B does not affect plant viability, growth and stress response. All in all, two discrete functions of AtDJ-1B respond differently to H₂O₂, and AtDJ-1B is not essential for plant development under stress.

Hydrogen peroxide (H₂O₂) is a key redox signaling molecule that selectively oxidizes cysteines on proteins. It can accomplish this even in the presence of highly efficient and abundant H₂O₂ scavengers, peroxiredoxins (Prdxs), as it is the Prdxs themselves that transfer oxidative equivalents to specific protein thiols on target proteins via their redox-relay functionality. The first evidence of a mammalian cytosolic Prdx-mediated redox-relay—Prdx1 with the kinase ASK1—was presented a decade ago based on the outcome of a co-immunoprecipitation experiment. A second such redox-relay—Prdx2:STAT3—soon followed, for which further studies provided insights into its specificity, organization, and mechanism. The Prdx1:ASK1 redox-relay, however, has never undergone such a characterization. Here, we combine cellular and in vitro protein–protein interaction methods to investigate the Prdx1:ASK1 interaction more thoroughly. We show that, contrary to the Prdx2:STAT3 redox-relay, Prdx1 interacts with ASK1 at elevated H₂O₂ concentrations, and that this interaction can happen independently of a scaffolding protein. We also provide evidence of a Prdx2:ASK1 interaction, and demonstrate that it requires a facilitator that, however, is not annexin A2. Our results reveal that cytosolic Prdx redox-relays can be organized in different ways and yet again highlight the differentiated roles of Prdx1 and Prdx2.