Fig. 4

Dystrophin loss impairs mitochondrial bioenergetics. A: Mitochondrial respiration of iPSC-derived cardiac fibroblasts was measured in three different DMD patients and three control patients. Mitochondrial stress test shows the OCR trace measured sequentially under basal conditions, following inhibition of ATP synthase (with oligomycin), uncoupling the electron transporter chain (ETC) with FCCP and blocking complex I and III with rotenone and antimycin A (Left graph). Basal respiration, maximal respiration, ATP production and spared respiratory capacity are reported in the left panels. Three independent experiments were performed. Non parametric t-test was applied to identify statistically significant differences between DMD and control. *p < 0.05, **p < 0.01. B: Western blot of respiratory complex subunits (OXPHOS) and quantification of experimental replicates of the six biological samples obtained from multiple differentiation batches. Non parametric t-test was applied to determine the statistically significant differences between DMD and control. *p < 0.05, **p < 0.01.C: Quantification of ATP levels in iPSC-derived cardiac fibroblasts from DMD and control patients (left panel). Cells were incubated for 60 min with sodium iodoacetate, a glycolysis inhibitor, to assess glycolysis-dependent ATP production (right panel). Two technical replicates from each of the three biological samples were performed independently. Non parametric t-test was applied to determine the statistically significant differences between DMD and control. *p < 0.05