Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?

These findings have provided the impetus for multiple studies investigating the purpose of this reversible, Prx hyperoxidation

Elizabeth A. Veal; Zoe E. Underwood; Lewis E. Tomalin; Brian A. Morgan; Ché S. Pillay

2017

Scholarcy highlights

  • In 2003, structural studies revealed that eukaryotic 2-Cys peroxiredoxins have evolved to be sensitive to inactivation of their thioredoxin peroxidase activity by hyperoxidation of their peroxide-reacting catalytic cysteine. This was accompanied by the unexpected discovery, that the sulfinylation of this cysteine was reversible in vivo and the identification of a new enzyme, sulfiredoxin, that had apparently co-evolved to reduce hyperoxidized 2-Cys Prx, restoring their peroxidase activity
  • These findings have provided the impetus for multiple studies investigating the purpose of this reversible, Prx hyperoxidation
  • Recent Advances: It has been suggested that inhibition of the thioredoxin peroxidase activity by hyperoxidation can both promote and inhibit peroxide signal transduction, depending on the context
  • Critical Issues: Here, we will review the evidence in support of each of these proposed functions, in view of the in vivo contexts in which Prx hyperoxidation occurs, and the role of sulfiredoxin
  • Future Directions: We provide a rationale, based on modeling and experimental studies, for why Prx hyperoxidation should be considered a suitable, early biomarker for damaging levels of reactive oxygen species
  • Global gene expression reveals an increase of HMGB1 and APEX1 proteins and their involvement in oxidative stress, apoptosis and inflammation pathways among beta‐thalassaemia intermedia and major phenotypes

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