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ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding

dc.contributor.authorKonno, Tasuku
dc.contributor.authorMelo, Eduardo Pinho
dc.contributor.authorLopes, Carlos
dc.contributor.authorMehmeti, Ilir
dc.contributor.authorLenzen, Sigurd
dc.contributor.authorRon, David
dc.contributor.authorAvezov, Edward
dc.date.accessioned2018-12-07T14:58:08Z
dc.date.available2018-12-07T14:58:08Z
dc.date.issued2015-10
dc.description.abstractThe 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 (H2O2) in the ER lumen. We report on a simple kinetic technique to track H2O2 equilibration between cellular compartments, suggesting that the ER is relatively isolated from cytosolic or mitochondria! H2O2 pools. Furthermore, expression of an ER-adapted catalase to degrade lumenal H2O2 attenuated PRDX4-mediated disulfide bond formation in cells lacking ERO1, whereas depletion of H2O2 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 H2O2 by PRDX4 and a parallel slow H2O2-independent pathway for disulfide formation.
dc.description.sponsorshipWellcome Trust (Wellcome) [084812]; European Commission (EU FP7 Beta-Bat) [277713]; Fundacao para a Ciencia e Tecnologia [PTDC/QUI-BIQ/119677/2010]; Japan Society for the Promotion of Science Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1083/jcb.201506123
dc.identifier.issn0021-9525
dc.identifier.issn1540-8140
dc.identifier.urihttp://hdl.handle.net/10400.1/11879
dc.language.isoeng
dc.peerreviewedyes
dc.publisherRockefeller University Press
dc.relationThe physiology and pathophysiology of unfolded protein responses.
dc.relationDevelopment of novel treatment strategies based on knowledge of cellular dysfunction in diabetes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectThiol oxidase
dc.subjectDisulfide formation
dc.subjectPeroxiredoxin
dc.subjectRedox
dc.subjectCells
dc.subjectIndicators
dc.subjectStress
dc.subjectSensor
dc.subjectEro1P
dc.subjectGene
dc.titleERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleThe physiology and pathophysiology of unfolded protein responses.
oaire.awardTitleDevelopment of novel treatment strategies based on knowledge of cellular dysfunction in diabetes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-BIQ%2F119677%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/WT/Cellular and Molecular Neuroscience/084812
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/277713/EU
oaire.citation.endPage259
oaire.citation.issue2
oaire.citation.startPage253
oaire.citation.titleJournal of Cell Biology
oaire.citation.volume211
oaire.fundingStream3599-PPCDT
oaire.fundingStreamCellular and Molecular Neuroscience
oaire.fundingStreamFP7
person.familyNamePinho Melo
person.familyNameLopes
person.givenNameEduardo
person.givenNameCarlos
person.identifier1443188
person.identifier.ciencia-id3C1C-C10C-1510
person.identifier.ciencia-id5B12-908A-21A2
person.identifier.orcid0000-0002-0974-8977
person.identifier.orcid0000-0002-6136-0478
person.identifier.ridK-4979-2015
person.identifier.scopus-author-id35566177900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/100010269
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameWellcome Trust
project.funder.nameEuropean Commission
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication21cb74bb-fd65-4da8-a95c-73d711c9c9d3
relation.isAuthorOfPublication.latestForDiscovery5fa1895f-5577-4652-961a-886ec9bf41b1
relation.isProjectOfPublication355a8acc-162a-4ab9-8628-cb6abfec6e02
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