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Disulphide production by Ero1alpha-PDI relay is rapid and effectively regulated

Appenzeller-Herzog, Christian and Riemer, Jan and Zito, Ester and Chin, King-Tung and Ron, David and Spiess, Martin and Ellgaard, Lars. (2010) Disulphide production by Ero1alpha-PDI relay is rapid and effectively regulated. The EMBO journal, Vol. 29, H. 19. pp. 3318-3329.

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Official URL: http://edoc.unibas.ch/dok/A5842476

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Abstract

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 Ero1alpha 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 Ero1alpha, 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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spiess)
UniBasel Contributors:Appenzeller, Christian and Spiess, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:0261-4189
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Dec 2015 10:49
Deposited On:14 Sep 2012 06:38

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