{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T09:56:16Z","timestamp":1756893376144,"version":"3.41.2"},"reference-count":62,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"AFM-T\u00e9l\u00e9thon","award":["19963"],"award-info":[{"award-number":["19963"]}]},{"name":"France Life Imaging network","award":["ANR-11-INBS-0006"],"award-info":[{"award-number":["ANR-11-INBS-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death. Here, we performed a time-course study of mitochondrial and muscular dysfunctions in 11- and 14-week-old Tfam KO mice, i.e. before and when mice are about to enter the terminal stage, respectively. Although force in the unfatigued state was reduced in Tfam KO mice compared to control littermates (wild type) only at 14\u2005weeks, during repeated submaximal contractions fatigue was faster at both ages. During fatiguing stimulation, total phosphocreatine breakdown was larger in Tfam KO muscle than in wild-type muscle at both ages, whereas phosphocreatine consumption was faster only at 14\u2005weeks. In conclusion, the Tfam KO mouse model represents a reliable model of lethal mitochondrial myopathy in which impaired mitochondrial energy production and premature fatigue occur before muscle weakness and early death.<\/jats:p>","DOI":"10.1242\/dmm.048981","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T09:45:35Z","timestamp":1628675135000},"source":"Crossref","is-referenced-by-count":7,"title":["Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle <i>Tfam-<\/i>knockout mouse model"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-1903","authenticated-orcid":false,"given":"Benjamin","family":"Chatel","sequence":"first","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CRMBM UMR CNRS 7339, 13385 Marseille, France"},{"name":"CellMade, 73370 Le-Bourget-du-Lac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3207-9537","authenticated-orcid":false,"given":"Sylvie","family":"Ducreux","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, UMR INSERM U1060\/INRA U1397, Universit\u00e9 Claude Bernard Lyon1, F-69310 Pierre-B\u00e9nite et F-69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-5160","authenticated-orcid":false,"given":"Zeina","family":"Harhous","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, UMR INSERM U1060\/INRA U1397, Universit\u00e9 Claude Bernard Lyon1, F-69310 Pierre-B\u00e9nite et F-69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-7007","authenticated-orcid":false,"given":"Nadia","family":"Bendridi","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM, INRA, INSA Lyon, Universit\u00e9 Claude Bernard Lyon 1, 69600 Oullins, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1711-7980","authenticated-orcid":false,"given":"Isabelle","family":"Varlet","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CRMBM UMR CNRS 7339, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-9964","authenticated-orcid":false,"given":"Augustin C.","family":"Ogier","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, Universit\u00e9 de Toulon, CNRS, LIS, 13397 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-8698","authenticated-orcid":false,"given":"Monique","family":"Bernard","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CRMBM UMR CNRS 7339, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-605X","authenticated-orcid":false,"given":"Julien","family":"Gondin","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoG\u00e8ne, UMR CNRS 5310 - INSERM U1217, Universit\u00e9 Claude Bernard Lyon 1, F-69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1587-2253","authenticated-orcid":false,"given":"Jennifer","family":"Rieusset","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, UMR INSERM U1060\/INRA U1397, Universit\u00e9 Claude Bernard Lyon1, F-69310 Pierre-B\u00e9nite et F-69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-3029","authenticated-orcid":false,"given":"H\u00e5kan","family":"Westerblad","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-0958","authenticated-orcid":false,"given":"David","family":"Bendahan","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, CRMBM UMR CNRS 7339, 13385 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-Marseille Universit\u00e9, CRMBM UMR CNRS 7339, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"2021091510473227300_DMM048981C1","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1007\/s13311-018-00674-4","article-title":"Diagnosis and treatment of mitochondrial myopathies","volume":"15","author":"Ahmed","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2021091510473227300_DMM048981C2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1152\/physrev.00015.2007","article-title":"Skeletal muscle fatigue: cellular mechanisms","volume":"88","author":"Allen","year":"2008","journal-title":"Physiol. 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