Figure 4. Mitochondrial activities in cells with the m.15992A>T mutation.

White bars = values obtained in control cells (C); black bars = values obtained in mutant cells (MT-TP) *p < 0.05, **p < 0.01 compared with the control group using the Mann-Whitney test or t test when data had a normal distribution according to the Shapiro-Wilk test. (A) Respiration rates measured in an Oroboros high-resolution respirometer and expressed as pmol·O₂·sec⁻¹·million cells⁻¹. Data shown as mean and SEM of 12 independent measurements for mutant fibroblasts (4 mutant lines derived from patients 1, 2, 3, and 4, each assayed 3 times), 50 for control fibroblasts (14 different control lines), 8 for mutant cybrids (6 different mutant lines derived from 2 different fibroblasts lines), and 15 for control cybrids (derived from 6 different control fibroblasts lines); basal = basal respiration calculated by subtracting the nonrespiratory oxygen consumption (with 1 mM KCN) from the respiration in culture medium with 1g/L glucose; ATP = respiration linked to ATP production calculated by subtracting the respiration under complete inhibition of ATP synthase by 1 µM oligomycin from the respiration in culture medium with 1 g/L glucose; Max = maximal respiratory capacity calculated by subtracting the nonrespiratory oxygen consumption (with 1 mM KCN) from the maximal respiration observed after uncoupling with successive additions of the protonophore carbonyl cyanide m-chlorophenyl hydrazone. (B) Maximal velocities analyzed by spectrophotometric assays on frozen mitochondrial pellets and expressed as nanomoles·min⁻¹·mg cellular proteins⁻¹. Data shown as mean and SEM of 8 independent measurements for mutant fibroblasts (4 mutant lines, each assayed twice), 9 for control fibroblasts (6 control lines), 7 for mutant cybrids (5 mutant lines), and 7 for control cybrids (6 different control lines); CI = respiratory complex I (rotenone sensitive NADH ubiquinone oxidoreductase activity); CII = respiratory complex II (succinate ubiquinone oxidoreductase activity); CIII = respiratory complex III (antimycin sensitive ubiquinol cytochrome c oxidoreductase activity); CIV = respiratory complex IV (cytochrome c oxidase activity); CV = ATP synthase (oligomycin-sensitive ATP hydrolysis activity); CS = citrate synthase. (C) Oxidative phosphorylation pathway (OXPHOS) maximal velocities normalized to the citrate synthase activity of the sample.