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Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.<\/jats:p>","DOI":"10.1083\/jcb.201909154","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T13:17:57Z","timestamp":1585747077000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Mitochondrial fragmentation enables localized signaling required for cell repair"],"prefix":"10.1083","volume":"219","author":[{"given":"Adam","family":"Horn","sequence":"first","affiliation":[{"name":"Children\u2019s National Health System, Center for Genetic Medicine Research, Washington, DC 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-7526","authenticated-orcid":true,"given":"Shreya","family":"Raavicharla","sequence":"additional","affiliation":[{"name":"Children\u2019s National Health System, Center for Genetic Medicine Research, Washington, DC 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonna","family":"Shah","sequence":"additional","affiliation":[{"name":"Children\u2019s National Health System, Center for Genetic Medicine Research, Washington, DC 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5405-6267","authenticated-orcid":true,"given":"Dan","family":"Cox","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-5185","authenticated-orcid":true,"given":"Jyoti K.","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Children\u2019s National Health System, Center for Genetic Medicine Research, Washington, DC 1"},{"name":"Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"2023072813242406600_bib1","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/ncb3560","article-title":"Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin","volume":"19","author":"Ban","year":"2017","journal-title":"Nat. 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