HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 53, 55341-55347, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/55341    most recent M411409200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jessop, C. E. Articles by Bulleid, N. J. Search for Related Content PubMed PubMed Citation Articles by Jessop, C. E. Articles by Bulleid, N. J. Social Bookmarking                      What's this?

Glutathione Directly Reduces an Oxidoreductase in the Endoplasmic Reticulum of Mammalian Cells^*

Catherine E. Jessop and Neil J. Bulleid

From the Faculty of Life Sciences, The Michael Smith Building, University of Manchester, Manchester, M13 9PT, United Kingdom

The formation of disulfide bonds is an essential step in the folding of many glycoproteins and secretory proteins. Non-native disulfide bonds are often formed between incorrect cysteine residues, and thus the cell has dedicated a family of oxidoreductases that are thought to isomerize non-native bonds. For an oxidoreductase to be capable of performing isomerization or reduction reactions, it must be maintained in a reduced state. Here we show that most of the oxidoreductases are predominantly reduced in vivo. Following oxidative stress the oxidoreductases are quickly reduced, demonstrating that a robust reductive pathway is in place in mammalian cells. Using ERp57 as a model we show that the reductive pathway is cytosol-dependent and that the component responsible for the reduction of the oxidoreductases is the low molecular mass thiol glutathione. In addition, ERp57 is not reduced following oxidative stress when inhibitors of glutathione synthesis or glutathione reduction are added to cells. Glutathione directly reduces ERp57 at physiological concentrations in vitro, and biotinylated glutathione forms a mixed disulfide with ERp57 in microsomes. Our results demonstrate that glutathione plays a direct role in the isomerization of disulfide bonds by maintaining the mammalian oxidoreductases in a reduced state.

Received for publication, October 6, 2004 , and in revised form, October 25, 2004.

^* This work was supported by Wellcome Trust Grants 65432 and 56493. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 44-161-275-5103; Fax: 44-161-275-5082; E-mail: neil.bulleid{at}man.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. E. Chambers, C. E. Jessop, and N. J. Bulleid Formation of a Major Histocompatibility Complex Class I Tapasin Disulfide Indicates a Change in Spatial Organization of the Peptide-loading Complex during Assembly J. Biol. Chem., January 25, 2008; 283(4): 1862 - 1869. [Abstract] [Full Text] [PDF]

				S. G. Santos, E. C. Campbell, S. Lynch, V. Wong, A. N. Antoniou, and S. J. Powis Major Histocompatibility Complex Class I-ERp57-Tapasin Interactions within the Peptide-loading Complex J. Biol. Chem., June 15, 2007; 282(24): 17587 - 17593. [Abstract] [Full Text] [PDF]

				J. D. Atkin, M. A. Farg, B. J. Turner, D. Tomas, J. A. Lysaght, J. Nunan, A. Rembach, P. Nagley, P. M. Beart, S. S. Cheema, et al. Induction of the Unfolded Protein Response in Familial Amyotrophic Lateral Sclerosis and Association of Protein-disulfide Isomerase with Superoxide Dismutase 1 J. Biol. Chem., October 6, 2006; 281(40): 30152 - 30165. [Abstract] [Full Text] [PDF]

				S. Dias-Gunasekara, M. van Lith, J. A. G. Williams, R. Kataky, and A. M. Benham Mutations in the FAD Binding Domain Cause Stress-induced Misoxidation of the Endoplasmic Reticulum Oxidoreductase Ero1beta J. Biol. Chem., September 1, 2006; 281(35): 25018 - 25025. [Abstract] [Full Text] [PDF]

				T. Solda, N. Garbi, G. J. Hammerling, and M. Molinari Consequences of ERp57 Deletion on Oxidative Folding of Obligate and Facultative Clients of the Calnexin Cycle J. Biol. Chem., March 10, 2006; 281(10): 6219 - 6226. [Abstract] [Full Text] [PDF]

				J. D. Rand and C. M. Grant The Thioredoxin System Protects Ribosomes against Stress-induced Aggregation Mol. Biol. Cell, January 1, 2006; 17(1): 387 - 401. [Abstract] [Full Text] [PDF]

				J. Haugstetter, T. Blicher, and L. Ellgaard Identification and Characterization of a Novel Thioredoxin-related Transmembrane Protein of the Endoplasmic Reticulum J. Biol. Chem., March 4, 2005; 280(9): 8371 - 8380. [Abstract] [Full Text] [PDF]