Fig. 2: Sporadic and familial ALS MNs show a hypo-oxidative and hyper-glycolytic metabolic profile.
From: ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation
a Metabolic flux plots of healthy and ALS patient-derived sorted neurons, where oxygen consumption rate (OCR) was measured as a function of time. The MitoStress assay was used to measure bioenergetics parameters, by adding Complex V inhibitor oligomycin, mitochondrial uncoupler FCCP, and Complexes I and III inhibitors rotenone and antimycin A (AA). b Basal respiration, ATP production, and spare respiration were calculated for sorted neurons from each of the cell lines and demonstrated reduced mitochondrial respiration in ALS MNs. c Metabolic flux plots of healthy and ALS patient-derived sorted neurons, where extracellular acidification rate (ECAR) was measured as a function of time. The Glycolysis stress assay was used to measure bioenergetics parameters, by adding glucose, Complex V inhibitor oligomycin, and hexokinase inhibitor 2-DG. d Basal acidification, glycolysis, and glycolytic capacity were calculated for sorted neurons from each of the cell lines and demonstrated elevated glycolysis in ALS MNs. e OCR measurements using the MitoStress assay were performed and calculated for cortical neurons derived from healthy, ALS, and diseased isogenic iPSCs at day 28. f Metabolic flux analyses were performed using the MitoStress assay. Basal respiration, ATP production, and spare respiration calculated for BJ-iPS, BJ-SOD1L144F, and BJ-TDP43G298S cortical neurons reveal no significant changes in basal respiration and ATP production. Likewise, healthy and ALS patient iPSC-derived cortical neurons reveal no significant changes in basal respiration and ATP production. g OCR measurements using the MitoStress assay were performed and calculated for cardiomyocytes derived from healthy, ALS, and diseased isogenic iPSCs at day 28. h Metabolic flux analyses were performed using the MitoStress assay. Basal respiration, ATP production, and spare respiration calculated for BJ-iPS, BJ-SOD1L144F, and BJ-TDP43G298S cardiomyocytes reveal no significant changes in basal respiration and ATP production. Likewise, healthy and ALS patient iPSC-derived cardiomyocytes reveal no significant changes in basal respiration and ATP production. ***p < 0.001, ns non-significant; one-way ANOVA, Tukey’s multiple comparisons post hoc test.
