{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:55:59Z","timestamp":1789131359276,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008280","name":"University of Angers","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008280","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Angers University Hospital"},{"name":"Union nationale des Aveugles et D\u00e9ficients visuels"},{"name":"Association contre les Maladies mitochondriales"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leber\u2019s hereditary optic neuropathy (LHON) is the most common disorder due to mitochondrial DNA mutations and complex I deficiency. It is characterized by an acute vision loss, generally in young adults, with a higher penetrance in males. How complex I dysfunction induces the peculiar LHON clinical presentation remains an unanswered question. To gain an insight into this question, we carried out a non-targeted metabolomic investigation using the plasma of 18 LHON patients, during the chronic phase of the disease, comparing them to 18 healthy controls. A total of 500 metabolites were screened of which 156 were accurately detected. A supervised Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) highlighted a robust model for disease prediction with a Q2 (cum) of 55.5%, with a reliable performance during the permutation test (cross-validation analysis of variance, P-value\u2009=\u20095.02284e\u221205) and a good prediction of a test set (P\u2009=\u20090.05). This model highlighted 10 metabolites with variable importance in the projection (VIP)\u2009&amp;gt;\u20090.8. Univariate analyses revealed nine discriminating metabolites, six of which were the same as those found in the Orthogonal Projections to Latent Structures Discriminant Analysis model. In total, the 13 discriminating metabolites identified underlining dietary metabolites (nicotinamide, taurine, choline, 1-methylhistidine and hippurate), mitochondrial energetic substrates (acetoacetate, glutamate and fumarate) and purine metabolism (inosine). The decreased concentration of taurine and nicotinamide (vitamin B3) suggest interesting therapeutic targets, given their neuroprotective roles that have already been demonstrated for retinal ganglion cells. Our results show a reliable predictive metabolomic signature in the plasma of LHON patients and highlighted taurine and nicotinamide deficiencies.<\/jats:p>","DOI":"10.1093\/hmg\/ddab013","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T12:22:14Z","timestamp":1610108534000},"page":"21-29","source":"Crossref","is-referenced-by-count":24,"title":["A plasma metabolomic signature of Leber hereditary optic neuropathy showing taurine and nicotinamide deficiencies"],"prefix":"10.1093","volume":"30","author":[{"given":"Cinzia","family":"Bocca","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Le Paih","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Chao de la Barca","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Kouassy Nzoughet","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 de Paris, CiTCoM, CNRS, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Amati-Bonneau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Blanchet","sequence":"additional","affiliation":[{"name":"Centre de Ressources Biologiques, BB-0033-00038, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"V\u00e9die","sequence":"additional","affiliation":[{"name":"Plateformes Centre de Ressources Biologiques et Tumoroth\u00e8que, BB-0033-00063, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"},{"name":"H\u00f4pital Europ\u00e9en Georges Pompidou, D\u00e9partement de Biochimie, Assistance Publique - H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"G\u00e9romin","sequence":"additional","affiliation":[{"name":"Plateformes Centre de Ressources Biologiques et Tumoroth\u00e8que, BB-0033-00063, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Simard","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Procaccio","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bonneau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lenaers","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Orssaud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle d'Ophtalmologie, CRMR Ophtara, H\u00f4pital Europ\u00e9en Georges Pompidou (HEGP), GH Paris Centre, Assistance Publique - H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"Service d'Ophtalmologie, Ophtara H\u00f4pital Necker-Enfants Malades, GH Paris Centre, AP-HP, 149, rue de S\u00e8vres, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Reynier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d'Angers, 49933 Angers, France"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"2021040906162039200_ref1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.5301\/ejo.5000055","article-title":"Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe","volume":"22","author":"Mascialino","year":"2011","journal-title":"Eur. 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