{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:39:26Z","timestamp":1787495966148,"version":"build-2736575974"},"reference-count":113,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"REGIONE PUGLIA-MALATTIE RARE-Petruzzella","award":["246-10 2019"],"award-info":[{"award-number":["246-10 2019"]}]},{"name":"Fondazione Opera Pia Monte di Piet\u00e0 e Confidenze, Molfetta"},{"name":"Italian Ministry of Health-Ricerca Corrente 2021"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In several cases of mitochondrial diseases, the underlying genetic and bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in mitochondrial dysfunction are well understood. However, there is still limited knowledge about the specific cellular outcomes and factors involved for each gene and mutation, which contributes to the lack of effective treatments for these disorders. This study focused on fibroblasts from a patient with Autosomal Dominant Optic Atrophy (ADOA) plus syndrome harboring a mutation in the Optic Atrophy 1 (OPA1) gene. By combining functional and transcriptomic approaches, we investigated the mitochondrial function and identified cellular phenotypes associated with the disease. Our findings revealed that fibroblasts with the OPA1 mutation exhibited a disrupted mitochondrial network and function, leading to altered mitochondrial dynamics and reduced autophagic response. Additionally, we observed a premature senescence phenotype in these cells, suggesting a previously unexplored role of the OPA1 gene in inducing senescence in ADOA plus patients. This study provides novel insights into the mechanisms underlying mitochondrial dysfunction in ADOA plus and highlights the potential importance of senescence in disease progression.<\/jats:p>","DOI":"10.1093\/hmg\/ddae008","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T09:27:14Z","timestamp":1704965234000},"page":"768-786","source":"Crossref","is-referenced-by-count":14,"title":["<i>OPA<\/i>\n                    1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy\n                    <i>plus<\/i>\n                    fibroblasts"],"prefix":"10.1093","volume":"33","author":[{"given":"Paola","family":"Zanfardino","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN) , University of study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Amati","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN) , University of study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation , Viale del Tirreno, 56128 Calambrone, Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon N","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Biosciences , Biotechnology, and Biopharmaceutics, University of study of Bari Aldo Moro, via Orabona 4, 70125, Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apollonia","family":"Tullo","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes , Bioenergetics and Molecular Biotechnologies (IBIOM), , Via G. Amendola 122\/O, 70126 Bari , Italy"},{"name":"National Research Council , Bioenergetics and Molecular Biotechnologies (IBIOM), , Via G. Amendola 122\/O, 70126 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN) , University of study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"D\u2019Erchia","sequence":"additional","affiliation":[{"name":"Department of Biosciences , Biotechnology, and Biopharmaceutics, University of study of Bari Aldo Moro, via Orabona 4, 70125, Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6549-0114","authenticated-orcid":false,"given":"Ernesto","family":"Picardi","sequence":"additional","affiliation":[{"name":"Department of Biosciences , Biotechnology, and Biopharmaceutics, University of study of Bari Aldo Moro, via Orabona 4, 70125, Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5769-8655","authenticated-orcid":false,"given":"Claudia","family":"Nesti","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation , Viale del Tirreno, 56128 Calambrone, Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo M","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation , Viale del Tirreno, 56128 Calambrone, Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-6033","authenticated-orcid":false,"given":"Vittoria","family":"Petruzzella","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN) , University of study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"2024042000562233800_ref1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","article-title":"The multifaceted contributions of mitochondria to cellular metabolism","volume":"20","author":"Spinelli","year":"2018","journal-title":"Nat Cell Biol"},{"key":"2024042000562233800_ref2","doi-asserted-by":"crossref","first-page":"18792","DOI":"10.1074\/jbc.M400920200","article-title":"Loss of the intermembrane space protein Mgm1\/OPA1 induces swelling and localized constrictions along the lengths of mitochondria","volume":"279","author":"Griparic","year":"2004","journal-title":"J Biol Chem"},{"key":"2024042000562233800_ref3","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1074\/jbc.RA119.010983","article-title":"The short variant of optic atrophy 1 (OPA1) improves cell survival under 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