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dc.contributor.authorKruppa, Antonina
dc.contributor.authorKishi-Itakura, Chieko
dc.contributor.authorMasters, Thomas A
dc.contributor.authorRorbach, Joanna E
dc.contributor.authorGrice, Guinevere L
dc.contributor.authorKendrick-Jones, John
dc.contributor.authorNathan, James
dc.contributor.authorMinczuk, Michal
dc.contributor.authorBuss, Folma
dc.date.accessioned2018-03-14T09:58:39Z
dc.date.available2018-03-14T09:58:39Z
dc.date.issued2018-02-26
dc.identifier.issn1534-5807
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/273981
dc.description.abstractMitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged mitochondria via its ubiquitin-binding domain. This myosin motor initiates the assembly of F-actin cages to encapsulate damaged mitochondria by forming a physical barrier that prevents refusion with neighboring populations. Loss of MYO6 results in an accumulation of mitophagosomes and an increase in mitochondrial mass. In addition, we observe downstream mitochondrial dysfunction manifesting as reduced respiratory capacity and decreased ability to rely on oxidative phosphorylation for energy production. Our work uncovers a crucial step in mitochondrial quality control: the formation of MYO6-dependent actin cages that ensure isolation of damaged mitochondria from the network.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHela Cells
dc.subjectPhagosomes
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectUbiquitin-Protein Ligases
dc.subjectMyosin Heavy Chains
dc.subjectUbiquitin
dc.subjectProtein Binding
dc.subjectAutophagy
dc.subjectActin Cytoskeleton
dc.subjectMitophagy
dc.titleMyosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
dc.typeArticle
prism.endingPage499.e6
prism.issueIdentifier4
prism.publicationDate2018
prism.publicationNameDev Cell
prism.startingPage484
prism.volume44
dc.identifier.doi10.17863/CAM.21053
dcterms.dateAccepted2018-01-08
rioxxterms.versionofrecord10.1016/j.devcel.2018.01.007
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-02
dc.contributor.orcidNathan, James [0000-0002-0248-1632]
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.contributor.orcidBuss, Folma [0000-0003-4457-3479]
dc.identifier.eissn1878-1551
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/K000888/1)
pubs.funder-project-idBritish Heart Foundation (PG/15/12/31280)
pubs.funder-project-idMichael J Fox Foundation (MJFF) (15669)
pubs.funder-project-idMedical Research Council (MR/N000048/1)
pubs.funder-project-idMedical Research Council (MC_U105697135)
pubs.funder-project-idWellcome Trust (102770/Z/13/Z)
pubs.funder-project-idMedical Research Council (MC_UU_00015/4)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/K001981/1)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (093026/Z/10/Z)
cam.issuedOnline2018-02-01
cam.orpheus.successThu Jan 30 12:59:04 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