{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T18:01:11Z","timestamp":1774375271754,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["ERP-2019-23671048"],"award-info":[{"award-number":["ERP-2019-23671048"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RP-2019-23671045"],"award-info":[{"award-number":["RP-2019-23671045"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Joint Programme on Rare Diseases","award":["ERP-2019-23671048"],"award-info":[{"award-number":["ERP-2019-23671048"]}]},{"name":"European Joint Programme on Rare Diseases","award":["RP-2019-23671045"],"award-info":[{"award-number":["RP-2019-23671045"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["ERP-2019-23671048"],"award-info":[{"award-number":["ERP-2019-23671048"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RP-2019-23671045"],"award-info":[{"award-number":["RP-2019-23671045"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mariani Foundation","award":["ERP-2019-23671048"],"award-info":[{"award-number":["ERP-2019-23671048"]}]},{"name":"Mariani Foundation","award":["RP-2019-23671045"],"award-info":[{"award-number":["RP-2019-23671045"]}]},{"name":"Italian Ministry of Health","award":["ERP-2019-23671048"],"award-info":[{"award-number":["ERP-2019-23671048"]}]},{"name":"Italian Ministry of Health","award":["RP-2019-23671045"],"award-info":[{"award-number":["RP-2019-23671045"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leber\u2019s hereditary optic neuropathy (LHON) is a disease that affects the optical nerve, causing visual loss. The diagnosis of LHON is mostly defined by the identification of three pathogenic variants in the mitochondrial DNA. Idebenone is widely used to treat LHON patients, but only some of them are responders to treatment. In our study, we assessed the maximal respiration rate (MRR) and other respiratory parameters in eight fibroblast lines from subjects carrying LHON pathogenic variants. We measured also the effects of idebenone treatment on cell growth and mtDNA amounts. Results showed that LHON fibroblasts had significantly reduced respiratory parameters in untreated conditions, but no significant gain in MRR after idebenone supplementation. No major toxicity toward mitochondrial function and no relevant compensatory effect in terms of mtDNA quantity were found for the treatment at the tested conditions. Our findings confirmed that fibroblasts from subjects harboring LHON pathogenic variants displayed impaired respiration, regardless of the disease penetrance and severity. Testing responsiveness to idebenone treatment in cultured cells did not fully recapitulate in vivo data. The in-depth evaluation of cellular respiration in fibroblasts is a good approach to evaluating novel mtDNA variants associated with LHON but needs further evaluation as a potential biomarker for disease prognosis and treatment responsiveness.<\/jats:p>","DOI":"10.3390\/ijms241612580","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"12580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber\u2019s Hereditary Optic Neuropathy (LHON) Subjects"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-3195","authenticated-orcid":false,"given":"Mirko","family":"Baglivo","sequence":"first","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-9929","authenticated-orcid":false,"given":"Alessia","family":"Nasca","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-6028","authenticated-orcid":false,"given":"Eleonora","family":"Lamantea","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2699-6325","authenticated-orcid":false,"given":"Stefano","family":"Vinci","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Spagnolo","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Marchet","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Prokisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen, 85764 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Catania","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Costanza","family":"Lamperti","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-3766","authenticated-orcid":false,"given":"Daniele","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. 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