Fig. 4: Metabolic rewiring of ScURA revealed by [U-¹³C]glutamine labelling.

a, Model for [U-¹³C]glutamine oxidation in WT cells (top), in cells expressing ScURA (middle) and in cells expressing ScURA with acute inhibition of the mETC (bottom). Some intermediate reactions have been omitted from the scheme for simplicity. b, Normalized intensity values of succinate and α-ketoglutarate relative to 143B WT cells (ordinary one-way ANOVA, Sidak’s multiple comparison test. Succinate: WT versus ScURA, P < 0.0001; WT + anti/myxo versus ScURA + anti/myxo, P = 0.0023; α-ketoglutarate: WT versus ScURA, P = 0.0031; WT versus WT + anti/myxo, P = 0.0385). c, Ratio of normalized intensity values of α-ketoglutarate to citrate, relative to 143B WT cells (ordinary one-way ANOVA, Dunnett’s multiple comparison test, WT versus ScURA, P = 0.0037; WT versus WT + anti/myxo, P = 0.0091; WT versus ScURA + anti/myxo, P < 0.0001). d, Mass isotopologue distribution of citrate, aspartate, malate, S-(2-succino)-cysteine (2-SC) and succinate from [U-¹³C]glutamine tracing in 143B cells. e, Percentage of labelled citrate, aspartate and malate relative to WT 143B cells (citrate, P < 0.0001; aspartate, P = 0.0475; malate, P < 0.0001). f, M+3 and m+4 labelling intensity of succinate in 143B WT and ScURA-expressing cells treated with anti/myxo (P = 0.0003). g, Scheme of generation and labelling of 2-SC from fumarate. h, M+3 and m+4 labelling intensity of 2-SC in 143B WT and ScURA-expressing cells treated with anti/myxo (P < 0.0001). In e, f and h: ordinary two-way ANOVA, Šidák’s multiple comparison test. Data are presented as means of n = 3 independent biological replicates; error bars, s.d. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05.

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