Figure 3
From: Gene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function
Mitochondrial dysfunction in neurons carrying the p.A30P SNCA mutation. (A) Bioenergetic profile showing oxygen consumption rate (OCR) of patient-derived neurons following a mitochondrial stress test under basal conditions and following the treatments of the ATP synthase inhibitor oligomycin (O, 1 µM), the oxidative phosphorylation uncoupler FCCP (F, 500 nM), and the electron transport chain inhibitors rotenone (Complex I) and antimycin A (Complex III) (R&A, 10 µM). The cumulative OCR profile is shown in ventral midbrain neurons differentiated for 30 days (n = 3). The rates of (B) Basal Respiration, (C) ATP production, (D) Non-mitochondrial respiration, (E) Coupling efficiency, (F) Maximum Respiration and (G) Proton Leak are shown. Each data point refers to individual values taken from a minimum of 12 replicates from 3 independent biological replicates. Mitochondrial reactive oxygen species measured by flow cytometry of (H) MitoSOX Red positive cells and (I) MitoSOX Red mean fluorescence intensity in typical “maturation” culture medium or with N2 media (without B27, trophic factors and antioxidants) for 4 h (n = 4). Each data point refers to 4 independent biological replicates. For all statistical analyses, an ordinary one-way ANOVA was performed using the Tukey post-hoc multiple comparison test. All graphs were plotted as mean ± SD. *p < 0.05, ** p < 0.01, ***p < 0.001 ****p < 0.0001.
