title: Lack of an efficient endoplasmic reticulum-localized recycling system protects peroxiredoxin IV from hyperoxidation.
abstract: 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 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 involving thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared with 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 peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation.
authors.affiliation: From the Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Cao
authors.forename: Suraj
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Bulleid
mesh_terms: D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D013879:Thioredoxins; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; D013880:Thioredoxin-Disulfide Reductase
keywords: Disulfide; Peroxiredoxin; Protein Isomerase; Thioredoxin; Thioredoxin Reductase