Protective mitochondrial fission induced by stress-responsive protein GJA1-20k

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dc.contributor.authorShimura, Daisukeen
dc.contributor.authorNuebel, Estheren
dc.contributor.authorBaum, Rachelen
dc.contributor.authorValdez, Steven E.en
dc.contributor.authorXiao, Shaohuaen
dc.contributor.authorWarren, Junco S.en
dc.contributor.authorPalatinus, Joseph A.en
dc.contributor.authorHong, TingTingen
dc.contributor.authorRutter, Jareden
dc.contributor.authorShaw, Robin M.en
dc.date.accessioned2023-01-17T14:11:08Zen
dc.date.available2023-01-17T14:11:08Zen
dc.date.issued2021-10-05en
dc.date.updated2023-01-14T14:36:39Zen
dc.description.abstractThe Connexin43 gap junction gene <i>GJA1</i> has one coding exon, but its mRNA undergoes internal translation to generate N-terminal truncated isoforms of Connexin43 with the predominant isoform being only 20 kDa in size (GJA1-20k). Endogenous GJA1-20k protein is not membrane bound and has been found to increase in response to ischemic stress, localize to mitochondria, and mimic ischemic preconditioning protection in the heart. However, it is not known how GJA1-20k benefits mitochondria to provide this protection. Here, using human cells and mice, we identify that GJA1-20k polymerizes actin around mitochondria which induces focal constriction sites. Mitochondrial fission events occur within about 45 s of GJA1-20k recruitment of actin. Interestingly, GJA1-20k mediated fission is independent of canonical Dynamin-Related Protein 1 (DRP1). We find that GJA1-20k-induced smaller mitochondria have decreased reactive oxygen species (ROS) generation and, in hearts, provide potent protection against ischemia-reperfusion injury. The results indicate that stress responsive internally translated GJA1-20k stabilizes polymerized actin filaments to stimulate non-canonical mitochondrial fission which limits ischemic-reperfusion induced myocardial infarction.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.7554/elife.69207en
dc.identifier.eissn2050-084Xen
dc.identifier.issn2050-084Xen
dc.identifier.orcidWarren, Junko [0000-0001-5231-4181]en
dc.identifier.otherPMC8492060en
dc.identifier.other69207 (PII)en
dc.identifier.pmid34608863en
dc.identifier.urihttp://hdl.handle.net/10919/113193en
dc.identifier.volume10en
dc.language.isoenen
dc.publishereLifeen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/34608863en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectGJA1-20ken
dc.subjectactin dynamicsen
dc.subjectcell biologyen
dc.subjecthumanen
dc.subjectischemia/reperfusionen
dc.subjectmitochondriaen
dc.subjectmitochondria dynamicsen
dc.subjectmouseen
dc.subjectorgan protectionen
dc.subjectCardiovascularen
dc.subjectHeart Diseaseen
dc.subjectHeart Disease - Coronary Heart Diseaseen
dc.subject1.1 Normal biological development and functioningen
dc.subject1 Underpinning researchen
dc.subject.meshMitochondriaen
dc.subject.meshMyocytes, Cardiacen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMyocardial Infarctionen
dc.subject.meshReactive Oxygen Speciesen
dc.subject.meshConnexin 43en
dc.subject.meshMaleen
dc.subject.meshHEK293 Cellsen
dc.subject.meshMitochondrial Dynamicsen
dc.titleProtective mitochondrial fission induced by stress-responsive protein GJA1-20ken
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherResearch Support, Non-U.S. Gov'ten
dc.type.otherresearch-articleen
dc.type.otherJournal Articleen
dc.type.otherResearch Support, N.I.H., Extramuralen
dcterms.dateAccepted2021-09-09en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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