17 Krylova T. Itkis Yu. Tsygankova P. Chistol D. Lyamzaev K. Tabakov V. Mikhaylova S. Nikitina N. Rudenskaya G. Murtazina A. Markova T. Semenova N. Buchinskaya N. Saifullina E.V. Aksyanova H. Sparber P. Andreeva N. Venediktova N. Ivanushkina A. Eliseeva D. Murakhovskaya Yu. Sheremet N. Zakharova E. mtDNA heteroplasmy LHON Leigh MELAS respirometry Scopus Web of Science Белый список 2025 2026-05-21 10.3390/ijms26104565 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES The m.13513G>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 strokelike 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>A mutation, classified according to the following phenotypes: Leigh syndrome (n = 12), MELAS (n = 2), and Leber’s 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>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’ phenotype, providing a solid foundation for the development of future gene therapies for mtDNA diseases. https://repo.bashgmu.ru/publication/5378 https://repo.bashgmu.ru/files/5571