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Disulphide production by Ero1α–PDI relay is rapid and effectively regulated
Author(s) -
AppenzellerHerzog Christian,
Riemer Jan,
Zito Ester,
Chin KingTung,
Ron David,
Spiess Martin,
Ellgaard Lars
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.203
Subject(s) - endoplasmic reticulum , protein disulfide isomerase , oxidoreductase , chemistry , glutathione , redox , golgi apparatus , isomerase , oxidative phosphorylation , compartment (ship) , kinetics , substrate (aquarium) , biochemistry , enzyme , biophysics , microbiology and biotechnology , biology , organic chemistry , physics , quantum mechanics , ecology , oceanography , geology
The molecular networks that control endoplasmic reticulum (ER) redox conditions in mammalian cells are incompletely understood. Here, we show that after reductive challenge the ER steady‐state disulphide content is restored on a time scale of seconds. Both the oxidase Ero1α and the oxidoreductase protein disulphide isomerase (PDI) strongly contribute to the rapid recovery kinetics, but experiments in ERO1‐deficient cells indicate the existence of parallel pathways for disulphide generation. We find PDI to be the main substrate of Ero1α, and mixed‐disulphide complexes of Ero1 primarily form with PDI, to a lesser extent with the PDI‐family members ERp57 and ERp72, but are not detectable with another homologue TMX3. We also show for the first time that the oxidation level of PDIs and glutathione is precisely regulated. Apparently, this is achieved neither through ER import of thiols nor by transport of disulphides to the Golgi apparatus. Instead, our data suggest that a dynamic equilibrium between Ero1‐ and glutathione disulphide‐mediated oxidation of PDIs constitutes an important element of ER redox homeostasis.