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We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation\u2013contraction coupling, providing a potential pathomechanism contributing to myopathies.<\/jats:p>","DOI":"10.1083\/jcb.201312066","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T03:46:52Z","timestamp":1398138412000},"page":"179-195","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":167,"title":["Mitochondrial fusion is frequent in skeletal muscle and supports excitation\u2013contraction coupling"],"prefix":"10.1083","volume":"205","author":[{"given":"Ver\u00f3nica","family":"Eisner","sequence":"first","affiliation":[{"name":"MitoCare Center, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lenaers","sequence":"additional","affiliation":[{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (INSERM) U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Hajn\u00f3czky","sequence":"additional","affiliation":[{"name":"MitoCare Center, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,4,21]]},"reference":[{"key":"2023072307491538600_bib1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fnmol.2013.00002","article-title":"Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics","volume":"6","author":"Akerboom","year":"2013","journal-title":"Front Mol Neurosci."},{"key":"2023072307491538600_bib2","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1083\/jcb.107.2.481","article-title":"Coupling membranes as energy-transmitting cables. 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