Fig. 2: The m.3243 A > G mtDNA mutation switches cell metabolism to a more glycolytic phenotype, resulting in redox imbalance.

a, b The growth rates of patient fibroblasts were measured under a range of different nutrient conditions (normalised to the growth rate of each cell line in regular cell media), showing a decrease of growth rate compared to controls at glucose concentrations of 5 and 1 mM (a, p < 0.0001) but not at low glutamine (b) concentrations (n = 6 culture wells for all conditions, three independent experiments). c Glucose uptake in patient fibroblasts was measured using the fluorescent glucose analogue, 2-NBDG, showing a significantly increased rate of glucose uptake in the patient fibroblasts (n = 14 culture wells, p < 0.0001). d, e NADH:NAD⁺ ratio of fibroblasts was measured using the reporter, SoNar, under basal conditions (n = 48, 46, 83 and 46 cells for Ctrl 1, Ctrl 2, Pat 1 and Pat 2 respectively) and after addition of pyruvate (200 μM, 30 min; n = 42, 33, 83 and 50 cells for Ctrl 1, Ctrl 2, Pat 1 and Pat 2 respectively; d) and quantified (e, p < 0.0001). Scale bar = 100 μm. f Lactate production (normalised to glucose consumption) was measured in the media of fibroblasts using CuBiAn and showed a significant increase in lactate release in the media of patient-derived cells (n = 4 independent biological samples, p = 0.0008). Source data were provided as a Source Data file. All data were represented as mean ± SD and data were analysed by one/two-way ANOVA with Tukey’s multiple comparisons test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).