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We crossed a\n                    <jats:italic>Ciona intestinalis<\/jats:italic>\n                    AOX transgene into RC complex III (cIII)\u2010deficient\n                    <jats:italic>Bcs1l<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>p.S78G<\/jats:italic>\n                    <\/jats:sup>\n                    knock\u2010in mice, displaying multiple visceral manifestations and premature death. The homozygotes expressing AOX were viable, and their median survival was extended from 210 to 590\u00a0days due to permanent prevention of lethal cardiomyopathy. AOX also prevented renal tubular atrophy and cerebral astrogliosis, but not liver disease, growth restriction, or lipodystrophy, suggesting distinct tissue\u2010specific pathogenetic mechanisms. Assessment of reactive oxygen species (ROS) production and damage suggested that ROS were not instrumental in the rescue. Cardiac mitochondrial ultrastructure, mitochondrial respiration, and pathological transcriptome and metabolome alterations were essentially normalized by AOX, showing that the restored electron flow upstream of cIII was sufficient to prevent cardiac energetic crisis and detrimental decompensation. These findings demonstrate the value of AOX, both as a mechanistic tool and a potential therapeutic strategy, for cIII deficiencies.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201809456","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T10:45:13Z","timestamp":1544438713000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Alternative oxidase\u2010mediated respiration prevents lethal mitochondrial cardiomyopathy"],"prefix":"10.1038","volume":"11","author":[{"given":"Jayasimman","family":"Rajendran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Purhonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saara","family":"Tegelberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli\u2010Pekka","family":"Smolander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rozman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Gailus\u2010Durner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hrabe de Angelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri","family":"Auvinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero","family":"Mervaala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard T","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marten","family":"Szibor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineta","family":"Fellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-7025","authenticated-orcid":false,"given":"Jukka","family":"Kallij\u00e4rvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,10]]},"reference":[{"key":"BFEMMM201809456_CR1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1096\/fj.05-3718com","volume":"19","author":"VJ Adlam","year":"2005","unstructured":"Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, Sammut IA (2005) Targeting an antioxidant to mitochondria decreases cardiac ischemia\u2010reperfusion injury. 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