Extended Data Fig. 6: Consequences of perturbed metabolism in complex II-inhibited AML cells.
a) Pathway Impact plot for steady state metabolites in MOLM-13 cells treated with DMSO or TTFA for 18 hr. Pathway Impact data and P values were calculated using Metaboanalyst software (Supplemental Table 3). b-d) Growth inhibition curves for (b) MOLM-13, (c) OCI-AML2 and (d) THP-1 cells cultured in the presence of increasing concentrations of DMG, DMKG or DMS. e) Glutamate secreted into glutamate-deficient media over 8 hr by OCI-AML2 cells cultured in DMSO or 200 μM TTFA. f) Viability of a panel of 8 AML cell lines cultured for 72 hr in amino-acid free RPMI1640 reconstituted with all amino acids (RPMI1640+AAs), devoid of all amino acids (RPMI1640-AAs), or with individual amino acid dropouts. Each point represents a cell line and is the average of n = 3 replicates for that cell line. g) Effect of Complex II inhibition on 13C6-glucose-derived carbon in glutathione (m + 2, from either glutamate or glycine). All data are shown as mean ± s.e.m. of n = 3 experiments unless otherwise specified. P value was calculated using an unpaired, two-tailed Student’s t-test.
