For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
23
references
 Top references
cited by
22
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      0
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      ERO1-independent production of H 2O 2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Tracking the kinetics of equilibration of H 2O 2 between compartments reveals unexpected isolation of the endoplasmic reticulum and hints at a hitherto unsuspected local source of peroxide.

          Abstract

          The endoplasmic reticulum (ER)–localized peroxiredoxin 4 (PRDX4) supports disulfide bond formation in eukaryotic cells lacking endoplasmic reticulum oxidase 1 (ERO1). The source of peroxide that fuels PRDX4-mediated disulfide bond formation has remained a mystery, because ERO1 is believed to be a major producer of hydrogen peroxide (H 2O 2) in the ER lumen. We report on a simple kinetic technique to track H 2O 2 equilibration between cellular compartments, suggesting that the ER is relatively isolated from cytosolic or mitochondrial H 2O 2 pools. Furthermore, expression of an ER-adapted catalase to degrade lumenal H 2O 2 attenuated PRDX4-mediated disulfide bond formation in cells lacking ERO1, whereas depletion of H 2O 2 in the cytosol or mitochondria had no similar effect. ER catalase did not effect the slow residual disulfide bond formation in cells lacking both ERO1 and PRDX4. These observations point to exploitation of a hitherto unrecognized lumenal source of H 2O 2 by PRDX4 and a parallel slow H 2O 2-independent pathway for disulfide formation.

          Related collections

          Most cited references23

          • Record: found
          • Abstract: found
          • Article: not found

          Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells.

          M Tiedge, S Lortz, J Drinkgern … (1997)
          Antioxidant enzyme expression was determined in rat pancreatic islets and RINm5F insulin-producing cells on the level of mRNA, protein, and enzyme activity in comparison with 11 other rat tissues. Although superoxide dismutase expression was in the range of 30% of the liver values, the expression of the hydrogen peroxide-inactivating enzymes catalase and glutathione peroxidase was extremely low, in the range of 5% of the liver. Pancreatic islets but not RINm5F cells expressed an additional phospholipid hydroperoxide glutathione peroxidase that exerted protective effects against lipid peroxidation of the plasma membrane. Regression analysis for mRNA and protein expression and enzyme activities from 12 rat tissues revealed that the mRNA levels determine the enzyme activities of the tissues. The induction of cellular stress by high glucose, high oxygen, and heat shock treatment did not affect antioxidant enzyme expression in rat pancreatic islets or in RINm5F cells. Thus insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression. Through stable transfection, however, we were able to increase catalase and glutathione peroxidase gene expression in RINm5F cells, resulting in enzyme activities more than 100-fold higher than in nontransfected controls. Catalase-transfected RINm5F cells showed a 10-fold greater resistance toward hydrogen peroxide toxicity, whereas glutathione peroxidase overexpression was much less effective. Thus inactivation of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin-producing cells. Overexpression of catalase may therefore be an effective means of preventing the toxic action of reactive oxygen species.
          Article 0 comments Cited 254 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Activation of the OxyR transcription factor by reversible disulfide bond formation.

            M Zheng, F Aslund, G Storz (1998)
            The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation. The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction.
            Article 0 comments Cited 207 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Generating disulfides enzymatically: reaction products and electron acceptors of the endoplasmic reticulum thiol oxidase Ero1p.

              Nimrod Heldman, Elvira Vitu, Colin Thorpe … (2006)
              Ero1p is a key enzyme in the disulfide bond formation pathway in eukaryotic cells in both aerobic and anaerobic environments. It was previously demonstrated that Ero1p can transfer electrons from thiol substrates to molecular oxygen. However, the fate of electrons under anaerobic conditions and the final fate of electrons under aerobic conditions remained obscure. To address these fundamental issues in the Ero1p mechanism, we studied the transfer of electrons from recombinant yeast Ero1p to various electron acceptors. Under aerobic conditions, reduction of molecular oxygen by Ero1p yielded stoichiometric hydrogen peroxide. Remarkably, we found that reduced Ero1p can transfer electrons to a variety of small and macromolecular electron acceptors in addition to molecular oxygen. In particular, Ero1p can catalyze reduction of exogenous FAD in solution. Free FAD is not required for the catalysis of dithiol oxidation by Ero1p, but it is sufficient to drive disulfide bond formation under anaerobic conditions. These findings provide insight into mechanisms for regenerating oxidized Ero1p and maintaining disulfide bond formation under anaerobic conditions in the endoplasmic reticulum.
              Article 0 comments Cited 98 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Biol
                Journal ID (iso-abbrev): J. Cell Biol
                Journal ID (publisher-id): jcb
                Journal ID (hwp): jcb
                Title: The Journal of Cell Biology
                Publisher: The Rockefeller University Press
                ISSN (Print): 0021-9525
                ISSN (Electronic): 1540-8140
                Publication date (Print): 26 October 2015
                Volume: 211
                Issue: 2
                Pages: 253-259
                Affiliations
                [1 ]University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust Medical Research Council Institute of Metabolic Science and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, CB2 0XY, UK
                [2 ]Center for Biomedical Research, Universidade do Algarve, Faro, Portugal 8005-139
                [3 ]Institute of Clinical Biochemistry, Hannover Medical School, 30625 Hannover, Germany
                Author notes
                Correspondence to Edward Avezov: ea347@ 123456cam.ac.uk ; or David Ron: dr360@ 123456medschl.cam.ac.uk
                Article
                Publisher ID: 201506123
                DOI: 10.1083/jcb.201506123
                PMC ID: 4621842
                PubMed ID: 26504166
                SO-VID: 782eb632-1c8a-4243-863f-aff2aa06bb35
                Copyright © © 2015 Konno et al.
                License:

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                Date received : 25 June 2015
                Date accepted : 18 September 2015
                Categories
                Subject: Research Articles
                Subject: Report

                ScienceOpen disciplines: Cell biology
                Data availability:
                ScienceOpen disciplines: Cell biology

                Comments

                Comment on this article