PT - JOURNAL ARTICLE
AU - Krylova T., 
AU - Itkis Yu., 
AU - Tsygankova P., 
AU - Chistol D., 
AU - Lyamzaev K., 
AU - Tabakov V., 
AU - Mikhaylova S., 
AU - Nikitina N., 
AU - Rudenskaya G., 
AU - Murtazina A., 
AU - Markova T., 
AU - Semenova N., 
AU - Buchinskaya N., 
AU - Saifullina E.V., 
AU - Aksyanova H., 
AU - Sparber P., 
AU - Andreeva N., 
AU - Venediktova N., 
AU - Ivanushkina A., 
AU - Eliseeva D., 
AU - Murakhovskaya Yu., 
AU - Sheremet N., 
AU - Zakharova E., 
TI - Exploring the Phenotypic Heterogeneity and Bioenergetic Profile of the m.13513G>A mtDNA Substitution: A Heteroplasmy Perspective
DP - 2026-05-21
TA - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
4100 - 10.3390/ijms26104565
SO - https://repo.bashgmu.ru/publication/5378
AB - 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.