{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:24:32Z","timestamp":1775175872252,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,20]],"date-time":"2015-12-20T00:00:00Z","timestamp":1450569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Mitochondrial respiration is regulated by multiple elaborate mechanisms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It has been shown that muscle specific O<jats:sub>2<\/jats:sub> binding protein, Myoglobin (Mb), is localized in mitochondria and interacts with respiratory chain complex IV, suggesting that Mb could be a factor that regulates mitochondrial respiration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we demonstrate that muscle mitochondrial respiration is improved by Mb overexpression via up\u2010regulation of complex IV activity in cultured myoblasts; in contrast, suppression of Mb expression induces a decrease in complex IV activity and mitochondrial respiration compared with the overexpression model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present data are the first to show the biological significance of mitochondrial Mb as a potential modulator of mitochondrial respiratory capacity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Mitochondria are important organelles for metabolism, and their respiratory capacity is a primary factor in the regulation of energy expenditure. Deficiencies of cytochrome <jats:italic>c<\/jats:italic> oxidase complex IV, which reduces O<jats:sub>2<\/jats:sub> in mitochondria, are linked to several diseases, such as mitochondrial myopathy. Moreover, mitochondrial respiration in skeletal muscle tissue tends to be susceptible to complex IV activity. Recently, we showed that the muscle\u2010specific protein myoglobin (Mb) interacts with complex IV. The precise roles of mitochondrial Mb remain unclear. Here, we demonstrate that Mb facilitates mitochondrial respiratory capacity in skeletal muscles. Although mitochondrial DNA copy numbers were not altered in Mb\u2010overexpressing myotubes, O<jats:sub>2<\/jats:sub> consumption was greater in these myotubes than that in mock cells (Mock <jats:italic>vs<\/jats:italic>. Mb\u2010Flag::GFP: state 4, 1.00\u00a0\u00b1\u00a00.09 <jats:italic>vs<\/jats:italic>. 1.77\u00a0\u00b1\u00a00.34; state 3, 1.00\u00a0\u00b1\u00a00.29; Mock: 1.60\u00a0\u00b1\u00a00.53; complex 2\u20103\u20104: 1.00\u00a0\u00b1\u00a00.30 <jats:italic>vs<\/jats:italic>. 1.50\u00a0\u00b1\u00a00.44; complex IV: 1.00\u00a0\u00b1\u00a00.14 <jats:italic>vs<\/jats:italic>. 1.87\u00a0\u00b1\u00a00.27). This improvement in respiratory capacity could be because of the activation of enzymatic activity of respiratory complexes. Moreover, mitochondrial respiration was up\u2010regulated in myoblasts transiently overexpressing Mb; complex IV activity was solely activated in Mb\u2010overexpressing myoblasts, and complex IV activity was decreased in the myoblasts in which Mb expression was suppressed by Mb\u2010siRNA transfection (Mb vector transfected <jats:italic>vs<\/jats:italic>. Mb vector, control siRNA transfected <jats:italic>vs<\/jats:italic>. Mb vector, Mb siRNA transfected: 0.15 <jats:italic>vs<\/jats:italic>. 0.15 <jats:italic>vs<\/jats:italic>. 0.06). Therefore, Mb enhances the enzymatic activity of complex IV to ameliorate mitochondrial respiratory capacity, and could play a pivotal role in skeletal muscle metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270824","type":"journal-article","created":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T11:40:52Z","timestamp":1448019652000},"page":"483-495","source":"Crossref","is-referenced-by-count":33,"title":["Myoglobin and the regulation of mitochondrial respiratory chain complex IV"],"prefix":"10.1113","volume":"594","author":[{"given":"Tatsuya","family":"Yamada","sequence":"first","affiliation":[{"name":"Faculty of Human Sciences Kanazawa University  Kanazawa 920\u20131192 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Takakura","sequence":"additional","affiliation":[{"name":"Faculty of Health and Sports Science Doshisha University  Kyotanabe 610\u20130394 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