Fig. 8

Primary fibroblasts derived from 4 patients carrying distinct pathogenetic variants in the FLVCR1 gene (P1-P3-P6 and P7), from 2 healthy individuals (C1 and C2), and from 2 asymptomatic carriers (HET1 and HET2) were analyzed. Choline supplementation was achieved by treating the cells with 1 mM choline chloride for 16 hours. Each dot in the graphs represents a biological replicate. Error bars in the graphs denote the standard error of the mean (SEM). A Citrate synthase activity upon choline supplementation. B α-ketoglutarate dehydrogenase activity upon choline supplementation. C Succinate dehydrogenase activity upon choline supplementation. D Malate dehydrogenase activity upon choline supplementation. E Activity of the individual ETC complexes I-IV upon choline supplementation. F Total activity of the ETC measured as nmol of reduced cytochrome C /minute upon choline supplementation. G Mitochondria ATP content upon choline supplementation. H Measurement of mitochondrial Thiobarbituric Acid Reactive Substance (TBARS), as index of lipid peroxidation upon choline supplementation. A–H n = 3 biological replicates for healthy individuals; n = 2 biological replicates for asymptomatic carriers; n = 4 biological replicates for patients. Two-way ANOVA analysis of variance was performed to compare healthy individuals and patients. * = P < 0.5; ** = P < 0.01; ***P = < 0.001; ****P = 0.0001.