Fig. 6. Indisulam modulates glutamine utilisation and mitochondrial oxidation.

a Schematic representation of enrichment of ¹³C derived from ¹³C₅-glutamine into TCA cycle intermediates detected by GC-MS. b–g KELLY PARENTAL (PAR), DCAF15^WT or DCAF15^KO cells were exposed to 10 µM indisulam in the presence of 2 mM ¹³C₅-glutamine for 24 h. Fraction of carbons labelled from ¹³C₅-glutamine in Citrate (b), Aspartate (c) and Malate (d). M + n: a metabolite with n carbon atoms labelled with ¹³C. Data are the mean of three independent experiments. Changes in M + 4 labelled Citrate (e), Aspartate (f) and Malate (g) following indisulam exposure (n = 3 independent experiments). h–j Lifetime measurements of MX-Xtra probe in KELLY DCAF15^WT (h) and DCAF15^KO (i) treated with VC (0.1% DMSO), 10 µM indisulam or 10 µM E7820. Representative data for n = 3 independent experiments. j Oxygen Consumption Rate (OCR) measures in a lifetime (µs) per h. Data are normalised to VC treatment (n = 3 independent experiments). k Mitochondrial Membrane Potential (MMP) of KELLY DCAF15^WT or DCAF15^KO cells treated with VC (0.1% DMSO), 10 µM indisulam or 10 µM E7820. Measured as JC-1 aggregates, normalised to VC. Data are presented as mean values ± SEM. Statistical analysis in e–g was determined by a two-sided unpaired t-test, and in j and k by a two-sided one-sample t-test. Source data is provided as a Source Data File.