GPx8 peroxidase prevents leakage of H2O2 from the endoplasmic reticulum.
Free Radic Biol Med
; 70: 106-16, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24566470
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peroxidasas
/
Estrés del Retículo Endoplásmico
/
Glutatión Peroxidasa
/
Peróxido de Hidrógeno
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Suiza