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This study was performed to determine whether a mitochondrial myopathy is associated with adjustments in skeletal muscle fiber-type composition.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Ten rats were treated with zidovudine, an antiretroviral nucleoside reverse transcriptase inhibitor that induces a myopathy by interfering with mitochondrial functions. Soleus muscles were examined after 21 weeks of treatment. Ten untreated rats served as controls.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Zidovudine induced a myopathy with mitochondrial DNA depletion, abnormalities in mitochondrial ultrastructure, and reduced cytochrome <jats:italic>c<\/jats:italic> oxidase activity. Mitochondrial DNA was disproportionally more diminished in type I compared with type II fibers, whereas atrophy predominated in type II fibers. Compared with those of controls, zidovudine-exposed soleus muscles contained an increased proportion (256%) of type II fibers, whereas neonatal myosin heavy chains remained repressed, indicating fiber-type transformation in the absence of regeneration. Microarray gene-expression analysis confirmed enhanced fast-fiber isoforms, repressed slow-fiber transcripts, and reduced neonatal fiber transcripts in the mitochondrial myopathy. Respiratory chain transcripts were diminished, whereas the enzymes of glycolysis and glycogenolysis were enhanced, indicating a metabolic adjustment from oxidative to glycolytic capacities. A coordinated regulation was found of transcription factors known to orchestrate type II fiber formation (upregulation of <jats:italic>MyoD, Six1, Six2, Eya1<\/jats:italic>, and <jats:italic>Sox6<\/jats:italic>, and downregulation of <jats:italic>myogenin<\/jats:italic> and <jats:italic>ERR\u03b3<\/jats:italic>).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>The type I to type II fiber transformation in mitochondrial myopathy implicates mitochondrial function as a new regulator of skeletal muscle fiber type.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4076","type":"journal-article","created":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T21:38:49Z","timestamp":1351546729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Muscle-fiber transdifferentiation in an experimental model of respiratory chain myopathy"],"prefix":"10.1186","volume":"14","author":[{"given":"Nils","family":"Venhoff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Lebrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana C","family":"Venhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Biss\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janbernd","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich A","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,10,29]]},"reference":[{"key":"3815_CR1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/ana.410270402","volume":"27","author":"AM Emslie-Smith","year":"1990","unstructured":"Emslie-Smith AM, Engel AG: Microvascular changes in early and advanced dermatomyositis: a quantitative study. 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