Fig. 2: Mutant cells undergo a metabolic shift towards glycolysis caused by cellular redox imbalance.
a, Heatmap of unlabeled steady-state abundance of select mitochondrial metabolites, arginine, argininosuccinate (AS) and terminal fumarate adducts succinylcysteine (succ.cys) and succinicGSH (succGSH) (n = 12–18 technical replicates over n = 6 biological replicates). FC, fold change. b, Labeling fate of 13C derived from 1-13C-glutamine. c, Malate m+1 abundance, derived from 1-13C-glutamine with indicated treatment (n = 11, 11, 11, 8, 8, 8, 6, 6 and 9 technical replicates over n = 4, 4, 4, 3, 3, 3, 3, 3 and 3 biological replicates). d, Heatmap of unlabeled steady-state metabolite abundances for select intracellular glycolytic intermediates and extracellular lactate (Ex. lactate) (n = 12–18 technical replicates over n = 6 biological replicates). e, Labeling fate of U-13C-glucose. f, Abundance of U-13C-glucose derived lactate m+3 with indicated treatment (n = 9, 9, 9, 9, 6 and 6 technical replicates over n = 3 biological replicates). g, Labeling fate of 2H derived from 4-2H1-glucose; mitoLbNOX not shown for clarity. h, Malate m+1 abundance, derived from 4-2H1-glucose with indicated treatment (n = 17, 17, 18, 9, 7, 8, 8, 7 and 5 technical replicates over n = 6, 6, 6, 3, 3, 3, 3, 3 and 2 biological replicates). i, IC50 curves for 2-deoxyglucose (n = 4 technical replicates). Representative result of three biological replicates is shown. P values were determined using a one-way ANOVA test with Sidak multiple comparisons test (a,d) or Fisher’s LSD Test (c,f,h). Measure of centrality, mean; error bars, s.d. *P < 0.05; **P < 0.01; ***P < 0.001. Number of replicates are described across conditions from left to right as presented. Heatmap representations of data for which asterisks are not present report non-significant changes.
