Fig. 3.

Mitochondrial O₂consumption and specific mitochondrial electron transport Complex IV activity is suppressed in DS fibroblasts; pharmacological inhibition of CBS with AOAA improves the bioenergetic phenotype of DS cells without significantly affecting the bioenergetics of control cells. (A): Rates of oxygen consumption rate (OCR) recorded before and after sequential addition of oligomycin (1 μM), FCCP (2 μM) and rotenone/antimycin A (0.5 μM) to the cells using the Agilent Seahorse XFe24 Analyzer. (B): Calculated mean values of basal respiration, proton leak, maximal respiration, spare respiratory capacity, ATP-linked respiration. (C): Calculated mitochondrial coupling efficiency. (D) & (E) Specific activity of mitochondrial Complex IV in permeabilized cells. (PMP depicts the administration of the Agilent Seahorse XF Plasma Membrane Permeabilizer, a proprietary reagent that permeabilizes intact cells in culture.) Each line and bar graph represents the mean ± SEM of n = 8 human euploid control fibroblasts and n = 8 DS fibroblasts, as summarized in Table 1. Dotted connecting lines in the bar graphs indicate the same cell from a specific donor with/without AOAA treatment (3 μM, 24 h). *p ≤ 0.05, **p ≤ 0.01 indicates significant differences between DSC untreated vs. CC untreated; #p ≤ 0.05 indicates significant differences between DSC + AOAA vs. DSC untreated.