{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T14:10:01Z","timestamp":1736345401775,"version":"3.32.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction and Aims<\/jats:title><jats:p>Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast\u2010twitch skeletal muscle\u2010specific mitochondrial transcription factor A knockout (<jats:italic>Tfam<\/jats:italic> KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in\u00a0vivo mitochondrial energy production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were treated with CsA for 4\u2009weeks, beginning at 12\u2009weeks (i.e., before the terminal disease phase). Hindlimb plantar flexor muscles were fatigued by 80 contractions (40\u2009Hz, 1.5\u2009s on, 6\u2009s off) while measuring force and energy metabolism using phosphorus\u201031 magnetic resonance spectroscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Force decreased at similar rates in <jats:italic>Tfam<\/jats:italic> KO mice with and without the CsA treatment, reaching 50% of the baseline value after ~14\u2009\u00b1\u20091 contractions, which was faster than in control mice (25\u2009\u00b1\u20091 contractions). Phosphocreatine (PCr) decreased to ~10% of the control concentration in <jats:italic>Tfam<\/jats:italic> KO mice, independent of the treatment, which was larger than the ~20% observed in control mice. The time constant of PCr recovery was higher in untreated <jats:italic>Tfam<\/jats:italic> KO than that in control muscle (+100%) and similar in untreated and CsA\u2010treated <jats:italic>Tfam<\/jats:italic> KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results do not support improved mitochondrial energy production as a mechanism underlying the prolonged lifespan of <jats:italic>Tfam<\/jats:italic> KO mitochondrial myopathy mice treated with CsA. Thus, other mechanisms must be involved, such as the previously observed CsA\u2010mediated protection against excessive mitochondrial Ca<jats:sup>2+<\/jats:sup> accumulation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28315","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T11:50:17Z","timestamp":1734954617000},"page":"265-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclosporine A Delays the Terminal Disease Stage in the <i>Tfam<\/i><scp>KO<\/scp> Mitochondrial Myopathy Mouse Model Without Improving Mitochondrial Energy Production"],"prefix":"10.1002","volume":"71","author":[{"given":"Benjamin","family":"Chatel","sequence":"first","affiliation":[{"name":"Aix\u2010Marseille Univ CNRS, CRMBM  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Varlet","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille Univ 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G\u00e9n\u00e9tique du Neurone et du Muscle, UMR CNRS 5261\u2014INSERM U1315 Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e5kan","family":"Westerblad","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bendahan","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille Univ CNRS, CRMBM  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-089X","authenticated-orcid":false,"given":"Charlotte","family":"Gineste","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille Univ CNRS, CRMBM  Marseille 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