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| http://purl.uniprot.org/citations/24566470 | http://www.w3.org/2000/01/rdf-schema#comment | "Unbalanced endoplasmic reticulum (ER) homeostasis (ER stress) leads to increased generation of reactive oxygen species (ROS). Disulfide-bond formation in the ER by Ero1 family oxidases produces hydrogen peroxide (H2O2) and thereby constitutes one potential source of ER-stress-induced ROS. However, we demonstrate that Ero1α-derived H2O2 is rapidly cleared by glutathione peroxidase (GPx) 8. In 293 cells, GPx8 and reduced/activated forms of Ero1α co-reside in the rough ER subdomain. Loss of GPx8 causes ER stress, leakage of Ero1α-derived H2O2 to the cytosol, and cell death. In contrast, peroxiredoxin (Prx) IV, another H2O2-detoxifying rough ER enzyme, does not protect from Ero1α-mediated toxicity, as is currently proposed. Only when Ero1α-catalyzed H2O2 production is artificially maximized can PrxIV participate in its reduction. We conclude that the peroxidase activity of the described Ero1α-GPx8 complex prevents diffusion of Ero1α-derived H2O2 within and out of the rough ER. Along with the induction of GPX8 in ER-stressed cells, these findings question a ubiquitous role of Ero1α as a producer of cytoplasmic ROS under ER stress."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.freeradbiomed.2014.01.018"xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/author | "Nagata K."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/author | "Ellgaard L."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/author | "Appenzeller-Herzog C."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/author | "Hansen H.G."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/author | "Ramming T."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/name | "Free Radic Biol Med"xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/pages | "106-116"xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/title | "GPx8 peroxidase prevents leakage of H2O2 from the endoplasmic reticulum."xsd:string |
| http://purl.uniprot.org/citations/24566470 | http://purl.uniprot.org/core/volume | "70"xsd:string |
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