{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:53:48Z","timestamp":1793051628812,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,15]],"date-time":"2019-06-15T00:00:00Z","timestamp":1560556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["282310-MyoPHAGY"],"award-info":[{"award-number":["282310-MyoPHAGY"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","award":["19524"],"award-info":[{"award-number":["19524"]}],"id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2010\/2011"],"award-info":[{"award-number":["PRIN 2010\/2011"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["Leducq"],"award-info":[{"award-number":["Leducq"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["17388"],"award-info":[{"award-number":["17388"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["RISE-2014 645648"],"award-info":[{"award-number":["RISE-2014 645648"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["STARTING GRANT"],"award-info":[{"award-number":["STARTING GRANT"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The maintenance of muscle mass and its ability to function relies on a bioenergetic efficient mitochondrial network. This network is highly impacted by fusion and fission events. We have recently shown that the acute deletion of the fusion protein Opa1 induces muscle atrophy, systemic inflammatory response, precocious epithelial senescence, and premature death that are caused by muscle-dependent secretion of FGF21. However, both fusion and fission machinery are suppressed in aging sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting. We generated inducible muscle-specific Opa1 and Drp1 double-knockout mice to address the physiological relevance of the concomitant impairment of fusion and fission machinery in skeletal muscle. Here we show that acute ablation of Opa1 and Drp1 in adult muscle causes the accumulation of abnormal and dysfunctional mitochondria, as well as the inhibition of autophagy and mitophagy pathways. This ultimately results in ER stress, muscle loss, and the reduction of force generation. However, the simultaneous inhibition of the fission protein Drp1 when Opa1 is absent alleviates FGF21 induction, oxidative stress, denervation, and inflammation rescuing the lethal phenotype of Opa1 knockout mice, despite the presence of any muscle weakness. Thus, the simultaneous inhibition of fusion and fission processes mitigates the detrimental effects of unbalanced mitochondrial fusion and prevents the secretion of pro-senescence factors.<\/jats:p>","DOI":"10.3390\/cells8060597","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T03:24:41Z","timestamp":1560741881000},"page":"597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles"],"prefix":"10.3390","volume":"8","author":[{"given":"Vanina","family":"Romanello","sequence":"first","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Biomedical Science, University of Padua, via G. Colombo 3, 35100 Padua, Italy"},{"name":"Myology Center, University of Padua, via G. Colombo 3, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scalabrin","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Biomedical Science, University of Padua, via G. Colombo 3, 35100 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Albiero","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Medicine\u2014DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Blaauw","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Biomedical Science, University of Padua, via G. Colombo 3, 35100 Padua, Italy"},{"name":"Myology Center, University of Padua, via G. Colombo 3, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-8928","authenticated-orcid":false,"given":"Luca","family":"Scorrano","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Biology, University of Padua, via U. Bassi 58B, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sandri","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine, via Orus 2, 35129 Padua, Italy"},{"name":"Department of Biomedical Science, University of Padua, via G. Colombo 3, 35100 Padua, Italy"},{"name":"Myology Center, University of Padua, via G. Colombo 3, 35100 Padova, Italy"},{"name":"Department of Medicine, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1113\/jphysiol.1993.sp019673","article-title":"Separate measures of ATP utilization and recovery in human skeletal muscle","volume":"465","author":"Blei","year":"1993","journal-title":"J. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1152\/jappl.1993.75.2.712","article-title":"Human muscle metabolism during intermittent maximal exercise","volume":"75","author":"Gaitanos","year":"1993","journal-title":"J. Appl. Physiol."},{"key":"ref_3","first-page":"422","article-title":"Mitochondrial Quality Control and Muscle Mass Maintenance","volume":"6","author":"Romanello","year":"2015","journal-title":"Front. 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