Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides*

Peroxiredoxins (Prxs) contain an active site cysteine that is sensitive to oxidation by H₂O₂. Mammalian cells express six Prx isoforms that are localized to various cellular compartments. The oxidized active site cysteine of Prx can be reduced by a cellular thiol, thus enabling Prx to function as a locally constrained peroxidase. Regulation of Prx via phosphorylation in response to extracellular signals allows the local accumulation of H₂O₂ and thereby enables its messenger function. The fact that the oxidation state of the active site cysteine of Prx can be transferred to other proteins that are less intrinsically susceptible to H₂O₂ also allows Prx to function as an H₂O₂ sensor.