biostudies-literaturePanja CNational Science Center of Poland9972https://www.ebi.ac.uk/biostudies/studies/S-EPMC10282124biostudies-literatureUnknown13(1)Defects in ATP synthase functioning due to the substitutions in its two mitochondrially encoded subunits a and 8 lead to untreatable mitochondrial diseases. Defining the character of variants in genes encoding these subunits is challenging due to their low frequency, heteroplasmy of mitochondrial DNA in patients' cells and polymorphisms of mitochondrial genome. We successfully used yeast S. cerevisiae as a model to study the effects of variants in MT-ATP6 gene and our research led to understand how eight amino acid residues substitutions impact the proton translocation through the channel formed by subunit a and c-ring of ATP synthase at the molecular level. Here we applied this approach to study the effects of the m.8403T>C variant in MT-ATP8 gene. The biochemical data from yeast mitochonScientific reportsAnalysis of MT-ATP8 gene variants reported in patients by modeling in silico and in yeast model organism.PMC102821242016/23/B/NZ3/02098Baranowska EKucharczyk RNiedzwiecka KPoznanski JPanja CfalseAnalysis of MT-ATP8 gene variants reported in patients by modeling in silico and in yeast model organism.Defects in ATP synthase functioning due to the substitutions in its two mitochondrially encoded subunits a and 8 lead to untreatable mitochondrial diseases. Defining the character of variants in genes encoding these subunits is challenging due to their low frequency, heteroplasmy of mitochondrial DNA in patients' cells and polymorphisms of mitochondrial genome. We successfully used yeast S. cerevisiae as a model to study the effects of variants in MT-ATP6 gene and our research led to understand how eight amino acid residues substitutions impact the proton translocation through the channel formed by subunit a and c-ring of ATP synthase at the molecular level. Here we applied this approach to study the effects of the m.8403T>C variant in MT-ATP8 gene. The biochemical data from yeast mitochon2023-01-01T00:00:00Z2023 Jun2026-05-29T05:48:20.716Z2024-11-13T21:30:13.459ZS-EPMC102821243734005910.1038/s41598-023-36637-9