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dc.contributor.authorPatel, Den
dc.contributor.authorRorbach, Jen
dc.contributor.authorDowes, Ken
dc.contributor.authorSzukszto, Men
dc.contributor.authorPekalski, Men
dc.contributor.authorMinczuk, Michalen
dc.date.accessioned2018-02-19T13:53:09Z
dc.date.available2018-02-19T13:53:09Z
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/273324
dc.description.abstractMammalian mitochondria can be transferred between cells both in culture and in vivo. There is evidence that isolated mitochondria enter cells by endocytosis, but the mechanism has not been fully characterised. We investigated the entry mechanism of isolated mitochondria into human osteosarcoma (HOS) cells. Initially we confirmed that respiratory-competent cells can be produced following incubation of HOS cells lacking mitochondrial DNA (mtDNA) with functional exogenous mitochondria and selection in a restrictive medium. Treatment of HOS cells with inhibitors of different endocytic pathways suggest that uptake of EGFP-labelled mitochondria occurs via an actin-dependent endocytic pathway which is consistent with macropinocytosis. We later utilised time-lapse microscopy to show that internalised mitochondria were found in large, motile cellular vesicles. Finally, we used confocal imaging to show that EGFP-labelled mitochondria colocalise with a macropinocytic cargo molecule during internalisation, HOS cells produce membrane ruffles interacting with external mitochondria during uptake and EGFP-labelled mitochondria are found within early macropinosomes inside cells. In conclusion our results are consistent with isolated mitochondria being internalised by macropinocytosis in HOS cells.
dc.description.sponsorshipThis work was supported by a grant from the Medical Research Council UK (MC_U105697135). We are grateful to Folma Buss for very helpful discussions during the course of this wor
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleMacropinocytotic entry of isolated mitochondria in epidermal growth factor-activated human osteosarcoma cellsen
dc.typeArticle
prism.number12886en
prism.publicationNameScientific Reportsen
prism.volume7en
dc.identifier.doi10.17863/CAM.20352
dcterms.dateAccepted2017-09-20en
rioxxterms.versionofrecord10.1038/s41598-017-13227-0en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-09-20en
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (1098529)
pubs.funder-project-idMRC (1236928)
pubs.funder-project-idMRC (MC_U105697135)
pubs.funder-project-idMRC (MC_UU_00015/4)
cam.issuedOnline2017-10-10en
cam.orpheus.successThu Jan 30 12:58:25 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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