Lack of an Efficient Endoplasmic Reticulum-localized Recycling System Protects Peroxiredoxin IV from Hyperoxidation [Cell Biology]

January 8th, 2014 by Cao, Z., Subramaniam, S., Bulleid, N. J.

Typical 2-cys peroxiredoxins are required to remove hydrogen peroxide from several different cellular compartments. Their activity can be regulated by hyperoxidation and consequent inactivation of the active site peroxidatic cysteine. Here we have developed a simple assay to quantify the hyperoxidation of peroxiredoxins. Hyperoxidation of peroxiredoxins can only occur efficiently in the presence of a recycling system usually based on thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared to either the cytosolic or mitochondrial enzymes. Each enzyme is equally sensitive to hyperoxidation in the presence of a robust recycling system. Our results demonstrate that the peroxiredoxin IV recycling in the ER is much less efficient than in the cytosol or mitochondria leading to the protection of peroxiredoxin IV from hyperoxidation.