Oxidation of peroxiredoxin-4 induces oligomerization and promotes interaction with proteins governing protein folding and endoplasmic reticulum stress
| Autor: | Vikas Anathy, Sheryl L. White, Ester Zito, Allison M. Manuel, Albert van der Vliet, Yvonne M. W. Janssen-Heininger, Evan Elko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PRDX peroxiredoxin Protein Folding PDI protein disulfide isomerase TXNDC5 thioredoxin domain–containing protein 5 Endoplasmic Reticulum Biochemistry MW molecular weight ERO1a endoplasmic reticulum oxidoreductase alpha Mice UPR unfolded protein response Protein disulfide-isomerase ER stress airway epithelial cells lung peroxiredoxin-4 Animals Epithelial Cells Lung Peroxiredoxins Protein Interaction Domains and Motifs Protein Multimerization Endoplasmic Reticulum Stress Chemistry P4HB SBP streptavidin-binding peptide Cell biology PDIA6 protein disulfide isomerase A6 ERO1 ER oxidoreductin 1 HSPA5 heat shock 70 kDa protein 5 H2O2 hydrogen peroxide P4HB prolyl 4-hydroxylase subunit beta Thioredoxin Research Article HMW high molecular weight ER endoplasmic reticulum 03 medical and health sciences TBuOOH tertbutyl hydroperoxide Heat shock protein IPF idiopathic pulmonary fibrosis Molecular Biology 030102 biochemistry & molecular biology Endoplasmic reticulum Protein Disulfide-Isomerase A6 Cell Biology 030104 developmental biology Unfolded protein response NEM N-ethyl maleimide Peroxiredoxin ERP44 endoplasmic reticulum resident protein 44 |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | 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 state and interacting partners. Herein, we addressed these questions via nonreducing Western blots, mass spectrometry, and site-directed mutagenesis. We report that the oxidation of PRDX4 in lung epithelial cells treated with tertbutyl hydroperoxide caused a shift of PRDX4 from monomer/dimer to high molecular weight (HMW) species, which contain PRDX4 modified with sulfonic acid residues (PRDX4-SO3), as well as of a complement of ER-associated proteins, including protein disulfide isomerases important in protein folding, thioredoxin domain–containing protein 5, and heat shock protein A5, a key regulator of the ER stress response. Mutation of any of the four cysteines in PRDX4 altered the HMW species in response to tertbutyl hydroperoxide as well as the secretion of PRDX4. We also demonstrate that the expression of ER oxidoreductase 1 alpha, which generates H2O2 in the ER, increased PRDX4 HMW formation and secretion. These results suggest a link between SO3 modification in the formation of HMW PRDX4 complexes in cells, whereas the association of key regulators of ER homeostasis with HMW oxidized PRDX4 point to a putative role of PRDX4 in regulating ER stress responses. |
| Databáze: | OpenAIRE |
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