Fig. 2: Synthetic lethality between PPP and OXPHOS is reduced by increased ME1 expression. | Nature Communications

Fig. 2: Synthetic lethality between PPP and OXPHOS is reduced by increased ME1 expression.

From: Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition

Fig. 2

a Growth curves of 143B cells treated with DMSO, Piericidin (100 nM), G6PDi PPP (50 uM), and the combination of both (n = 3 biological replicates). Heat map showing intracellular levels of water-soluble metabolites in 143B cells treated with the indicated inhibitors for 48 h (b) and relative levels of dihydroxyacetone phosphate (c), D-sedoheptulose-1,7-bisphosphate (d) and NADPH/NADP+ ratio (e) (n = 3 biological replicates). f NADPH/NADP+ ratio at 24 and 72 h in 143B cells treated with DMSO, Piericidin (100 nM), G6PDi PPP (50 uM), and the combination of both (n = 3). g Relative reactive oxygen species (ROS) levels measured using dichlorodihydrofluorescein diacetate (H2DCFDA) in 143B cells treated with DMSO or Piericidin (100 nM) plus G6PDi (50 uM) (n = 3). h Cell number at 72 h in 143B cells overexpressing ME1 or IDH1 and treated with DMSO or Piericidin (100 nM) plus G6PDi (50 uM) (n = 3 biological replicates). i Heat map showing intracellular levels of TCA cycle associated metabolites analyzed by LC-MS in DMSO-treated or Piericidin-treated (100 nM) 143B cells for 24 h (n = 3). j Relative reactive oxygen species (ROS) levels in WT and IDH1 overexpressing 143B cells treated with DMSO or Piericidin (100 nM) plus G6PDi (50 uM) and supplemented with 2 mM trimethyl citrate (n = 3 biological replicates). Data are presented as means ± SEM. The statistical significance of the differences between groups was determined by two-wayANOVA (a, c, d, e, f, g, h and j). n.s not significant. Pier Piericidin, TM-Citrate Trimethyl citrate. Source data are provided as a Source Data file.

Back to article page