Fig. 8.

Mitochondrial respiration and ER-derived Ca²⁺ signaling are impaired in mutant FUS iPSC-derived OPCs. a, c Oxygen consumption rate (OCR) throughout the mitochondrial respiration in FUS^R521H OPCs (a) and FUS^P525L OPCs (c) and their respective isogenic controls (N ≥ 8). The time points of adding mitochondrial inhibitors to the media for evaluating respiratory parameters are indicated by arrows. b, d Basal respiration, maximal respiration, ATP production, and spare respiratory capacity in FUS^R521H OPCs (b) and FUS^P525L OPCs (d) and their respective isogenic controls. e, i Representative Ca²⁺ traces following 10 μM ATP stimulation (arrow) in FUS^R521H OPCs (e) and FUS^P525L OPCs (i) and their respective isogenic controls loaded with Cal-520. f, h Quantitative data of the corresponding AUC and peak after 10 μM ATP stimulation (N = 8). g, k Representative Ca²⁺ traces following 10 μM Ach stimulation (arrow) in FUS^R521H OPCs (g) and FUS^P525L OPCs (k) and their respective isogenic controls. h, l Quantitative data of the corresponding AUC and peak after 10 μM Ach stimulation (N = 8). Statistical analyses were performed by unpaired two-tailed t tests to compare mutant FUS OPCs and their control. Data are represented as mean ± SD. *p < 0.05 **p < 0.01 ***p < 0.001 ****p < 0.0001