Hyperoxidation of Peroxiredoxins and Effects on Physiology of Drosophila

The catalytic activity of peroxiredoxins (Prx) is determined by the conserved peroxidatic cysteine (Cys(P)), which reacts with peroxides to form sulfenic acid (Cys-SOH). Under conditions of oxidative stress, Cys(P) is oxidized to catalytically inactive sulfinic (Cys-SO(2)) and sulfonic (Cys-SO(3)) forms. The Cys-SO(2) form can be reduced in a reaction catalyzed by sulfiredoxin (Srx). To explore the physiological significance of peroxiredoxin overoxidation, we investigated daily variations in the oxidation state of 2-Cys peroxiredoxins in flies of different ages, or under conditions when the pro-oxidative load is high. We found no statistically significant changes in the 2-Cys Prxs monomer:dimer ratio, which indirectly reflects changes in the Prx catalytic activity. However, we found daily variations in Prx-SO(2/3) that were more pronounced in older flies as well as in flies lacking Srx. Unexpectedly, the srx mutant flies did not exhibit a diminished survivorship under normal or oxidative stress conditions. Moreover, the srx mutant was characterized by a higher physiological activity. In conclusion, catalytically inactive forms of Prx-SO(2/3) serve not only as a marker of cellular oxidative burden, but may also play a role in an adaptive response, leading to a positive effect on the physiology of Drosophila melanogaster.