{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:07:34Z","timestamp":1791223654714,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The m.13513G&gt;A (p.Asp393Asn) substitution in the MT-ND5 (Mitochondrially Encoded NADH\/Ubiquinone Oxidoreductase Core Subunit 5) gene is a common pathogenic variant associated with primary mitochondrial disorders. It frequently causes Leigh syndrome and mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). In this study, we present clinical data, heteroplasmy levels in various tissues (blood, urine, and skin fibroblasts), and bioenergetic characteristics from a cohort of 20 unrelated patients carrying the m.13513G&gt;A mutation, classified according to the following phenotypes: Leigh syndrome (n = 12), MELAS (n = 2), and Leber\u2019s hereditary optic neuropathy (LHON, n = 6). We observed a significant correlation between high respiratory ratios and heteroplasmy levels in fibroblast cell lines of the patients. Furthermore, fibroblast cell lines with heteroplasmy levels exceeding 55% exhibited markedly reduced mitochondrial membrane potential. These findings contribute to a better understanding of the clinical and bioenergetic profiles of patients with m.13513G&gt;A-variant-related phenotypes across different heteroplasmy levels, based on data from a single genetic center. Our data suggest that even a slight shift in heteroplasmy can improve cellular function and, consequently, the patients\u2019 phenotype, providing a solid foundation for the development of future gene therapies for mtDNA diseases.<\/jats:p>","DOI":"10.3390\/ijms26104565","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:58:07Z","timestamp":1747047487000},"page":"4565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Phenotypic Heterogeneity and Bioenergetic Profile of the m.13513G&gt;A mtDNA Substitution: A Heteroplasmy Perspective"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7197-3497","authenticated-orcid":false,"given":"Tatiana","family":"Krylova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Itkis","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-3609","authenticated-orcid":false,"given":"Polina","family":"Tsygankova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-7375","authenticated-orcid":false,"given":"Denis","family":"Chistol","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-8031","authenticated-orcid":false,"given":"Konstantin","family":"Lyamzaev","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"},{"name":"The \u201cRussian Clinical Research Center for Gerontology\u201d of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 129226 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Tabakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Mikhaylova","sequence":"additional","affiliation":[{"name":"Russian Children\u2019s Clinical Hospital, 119571 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Nikitina","sequence":"additional","affiliation":[{"name":"State Autonomous Healthcare Institution of the Sverdlovsk Region \u00abClinical and Diagnostic Center \u2018\u2018Maternal and Child Health 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Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-045X","authenticated-orcid":false,"given":"Natalia","family":"Semenova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2335-3023","authenticated-orcid":false,"given":"Natalia","family":"Buchinskaya","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), 194044 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Saifullina","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, 450008 Ufa, 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Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1316-0689","authenticated-orcid":false,"given":"Natalia","family":"Venediktova","sequence":"additional","affiliation":[{"name":"Research Institute of Eye Diseases, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Ivanushkina","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Budgetary Healthcare Institution City Clinic No. 14, 194021 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-927X","authenticated-orcid":false,"given":"Daria","family":"Eliseeva","sequence":"additional","affiliation":[{"name":"Research Center of Neurology, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Murakhovskaya","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, the Department of Ophthalmology, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Sheremet","sequence":"additional","affiliation":[{"name":"Research Institute of Eye Diseases, 119021 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Valenti, D., and Vacca, R. (2022). Primary and Secondary Mitochondrial Diseases: Etiologies and Therapeutic Strategies. J. Clin. 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