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dc.contributor.authorSim, Jingweien
dc.contributor.authorCowburn, Andrewen
dc.contributor.authorPalazon, Asisen
dc.contributor.authorMadhu, Basettien
dc.contributor.authorTyrakis, Petros Aen
dc.contributor.authorMacías, Daviden
dc.contributor.authorBargiela, David Men
dc.contributor.authorPietsch, Sandraen
dc.contributor.authorGralla, Michaelen
dc.contributor.authorEvans, Colin Een
dc.contributor.authorKittipassorn, Thaksaonen
dc.contributor.authorChey, Yu CJen
dc.contributor.authorMendes Branco, Cristina Brancoen
dc.contributor.authorRundqvist, Heleneen
dc.contributor.authorPeet, Daniel Jen
dc.contributor.authorJohnson, Randallen
dc.date.accessioned2018-04-10T09:23:16Z
dc.date.available2018-04-10T09:23:16Z
dc.date.issued2018-04en
dc.identifier.issn1550-4131
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274727
dc.description.abstractAnimals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia.
dc.format.mediumPrinten
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMiceen
dc.subjectOxygenen
dc.subjectMixed Function Oxygenasesen
dc.subjectProcollagen-Proline Dioxygenaseen
dc.subjectAdaptation, Physiologicalen
dc.subjectSignal Transductionen
dc.subjectCell Hypoxiaen
dc.subjectTranscription, Geneticen
dc.subjectGene Expression Regulationen
dc.subjectGlycolysisen
dc.subjectOxygen Consumptionen
dc.subjectMaleen
dc.subjectVon Hippel-Lindau Tumor Suppressor Proteinen
dc.subjectHypoxia-Inducible Factor-Proline Dioxygenasesen
dc.titleThe Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.en
dc.typeArticle
prism.endingPage913.e7
prism.issueIdentifier4en
prism.publicationDate2018en
prism.publicationNameCell metabolismen
prism.startingPage898
prism.volume27en
dc.identifier.doi10.17863/CAM.21863
dcterms.dateAccepted2018-02-20en
rioxxterms.versionofrecord10.1016/j.cmet.2018.02.020en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-04en
dc.contributor.orcidSim, Jingwei [0000-0002-6009-5684]
dc.contributor.orcidCowburn, Andrew [0000-0001-9145-4275]
dc.contributor.orcidPalazon, Asis [0000-0002-7172-7229]
dc.contributor.orcidMacías, David [0000-0002-8676-1964]
dc.contributor.orcidEvans, Colin E [0000-0002-9251-357X]
dc.contributor.orcidKittipassorn, Thaksaon [0000-0001-9854-2905]
dc.contributor.orcidChey, Yu CJ [0000-0001-7553-5163]
dc.contributor.orcidMendes Branco, Cristina Branco [0000-0001-6953-4922]
dc.contributor.orcidRundqvist, Helene [0000-0002-5617-9076]
dc.contributor.orcidJohnson, Randall [0000-0002-4084-6639]
dc.identifier.eissn1932-7420
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (092738/Z/10/Z)
pubs.funder-project-idBreast Cancer Campaign (2014MaySF275)
pubs.funder-project-idNational Cancer Institute (NCI) (R01CA153983)
pubs.funder-project-idEuropean Commission (331756)
pubs.funder-project-idWellcome Trust (214283/Z/18/Z)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International