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Endoplasmic reticulum: reduced and oxidized glutathione revisited

Birk, Julia and Meyer, Mariangela and Aller, Isabel and Hansen, Henning G. and Odermatt, Alex and Dick, Tobias P. and Meyer, Andreas J. and Appenzeller-Herzog, Christian. (2013) Endoplasmic reticulum: reduced and oxidized glutathione revisited. Journal of Cell Science, 126. pp. 1604-1617.

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Official URL: https://edoc.unibas.ch/64505/

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Abstract

The reducing power of glutathione, expressed by its reduction potential EGSH, is an accepted measure for redox conditions in a given cell compartment. In the endoplasmic reticulum (ER), EGSH is less reducing than elsewhere in the cell. However, attempts to determine EGSH(ER) have been inconsistent and based on ineligible assumptions. Using a codon-optimized and evidently glutathione-specific glutaredoxin-coupled redox-sensitive green fluorescent protein (roGFP) variant, we determined EGSH(ER) in HeLa cells as -208±4 mV (at pH 7.0). At variance with existing models, this is not oxidizing enough to maintain the known redox state of protein disulfide isomerase family enzymes. Live-cell microscopy confirmed ER hypo-oxidation upon inhibition of ER Ca(2+) import. Conversely, stressing the ER with a glycosylation inhibitor did not lead to more reducing conditions, as reported for yeast. These results, which for the first time establish the oxidative capacity of glutathione in the ER, illustrate a context-dependent interplay between ER stress and EGSH(ER). The reported development of ER-localized EGSH sensors will enable more targeted in vivo redox analyses in ER-related disorders.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Appenzeller-Herzog, Christian and Odermatt, Alex and Birk, Julia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Company of Biologists
ISSN:0021-9533
e-ISSN:1477-9137
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:24 Aug 2018 08:45
Deposited On:24 Aug 2018 08:45

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