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Oxidation of peroxiredoxin-4 induces oligomerization and promotes interaction with endoplasmic reticulum proteins

ABSTRACT: The family of peroxiredoxins catalyzes the reduction of hydrogen peroxide (H2O2). Peroxiredoxin 4 (PRDX4) is the only peroxiredoxin located within the endoplasmic reticulum (ER) and is the highest expressed ER H2O2 scavenger. PRDX4 has emerged as an important player in numerous diseases and its over-oxidation is a potential indicator of ER redox stress. The interactome of PRDX4 as well as the dynamics of its oligomerization have largely been unstudied. Therefore, the goal of this study was to determine the effect of oxidation on PRDX4 oligomerization and interaction with binding partners. We report that the oxidation of PRDX4 in lung epithelial cells treated with tertbutyl hydroperoxide (TBuOOH) caused a shift of PRDX4 from monomer/dimer to high molecular weight(HMW) species which are composed of PRDX4 containing sulfonic acid residues (PRDX4-SO3) as well as a complement of ER-associated proteins. Treatment of recombinant PRDX4 with TBuOOH also led to HMW complexes, showing that interactions with client proteins are not required for PRDX4 HMW complex formation.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Epithelial Cell, Cell Culture

SUBMITTER: Evan Elko

LAB HEAD: Yvonne Janssen-Heininger

PROVIDER: PXD024687 | Pride | 2021-09-10

REPOSITORIES: Pride

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Oxidation of peroxiredoxin-4 induces oligomerization and promotes interaction with proteins governing protein folding and endoplasmic reticulum stress.

Elko Evan A EA Manuel Allison M AM White Sheryl S Zito Ester E van der Vliet Albert A Anathy Vikas V Janssen-Heininger Yvonne M W YMW

The Journal of biological chemistry 20210101

Peroxiredoxins (PRDXs) catalyze the reduction of hydrogen peroxide (H2O2). PRDX4 is the only peroxiredoxin located within the endoplasmic reticulum (ER) and is the most highly expressed H2O2 scavenger in the ER. PRDX4 has emerged as an important player in numerous diseases, such as fibrosis and metabolic syndromes, and its overoxidation is a potential indicator of ER redox stress. It is unclear how overoxidation of PRDX4 governs its oligomerization sta ...[more]

PMID: 33895140

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