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Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects

Leber’s 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...

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Autores principales: Baglivo, Mirko, Nasca, Alessia, Lamantea, Eleonora, Vinci, Stefano, Spagnolo, Manuela, Marchet, Silvia, Prokisch, Holger, Catania, Alessia, Lamperti, Costanza, Ghezzi, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454080/
https://www.ncbi.nlm.nih.gov/pubmed/37628761
http://dx.doi.org/10.3390/ijms241612580
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author Baglivo, Mirko
Nasca, Alessia
Lamantea, Eleonora
Vinci, Stefano
Spagnolo, Manuela
Marchet, Silvia
Prokisch, Holger
Catania, Alessia
Lamperti, Costanza
Ghezzi, Daniele
author_facet Baglivo, Mirko
Nasca, Alessia
Lamantea, Eleonora
Vinci, Stefano
Spagnolo, Manuela
Marchet, Silvia
Prokisch, Holger
Catania, Alessia
Lamperti, Costanza
Ghezzi, Daniele
author_sort Baglivo, Mirko
collection PubMed
description Leber’s 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.
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spelling pubmed-104540802023-08-26 Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects Baglivo, Mirko Nasca, Alessia Lamantea, Eleonora Vinci, Stefano Spagnolo, Manuela Marchet, Silvia Prokisch, Holger Catania, Alessia Lamperti, Costanza Ghezzi, Daniele Int J Mol Sci Communication Leber’s 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. MDPI 2023-08-08 /pmc/articles/PMC10454080/ /pubmed/37628761 http://dx.doi.org/10.3390/ijms241612580 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Baglivo, Mirko
Nasca, Alessia
Lamantea, Eleonora
Vinci, Stefano
Spagnolo, Manuela
Marchet, Silvia
Prokisch, Holger
Catania, Alessia
Lamperti, Costanza
Ghezzi, Daniele
Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title_full Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title_fullStr Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title_full_unstemmed Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title_short Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects
title_sort evaluation of mitochondrial dysfunction and idebenone responsiveness in fibroblasts from leber’s hereditary optic neuropathy (lhon) subjects
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454080/
https://www.ncbi.nlm.nih.gov/pubmed/37628761
http://dx.doi.org/10.3390/ijms241612580
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