Fig. 3

VEN-RE cells were deficient in mitochondrial respiration. a Mitochondrial ND-1 DNA expression levels were detected by RT-PCR and normalized to HGB levels in the indicated parental and VEN-RE cells. **P < 0.005. b Number of mitochondria in five randomly selected parental and VEN-RE cells in different fields under transmission electron microscopy (TEM). ***P < 0.0005. c TEM images of mitochondrial morphology. Areas marked in red are enlarged in the insets on each panel. Scale bars indicate 2 μm in the larger windows and 500 nm in the insets. d Results of Seahorse assays showing oxygen consumption rate (OCR) with the indicated concentrations of FCCP) in parental (dotted lines) and VEN-RE MOLM-13 cells (solid lines). e Electron transport chain complex II activity in parental and VEN-RE cell lines. ****P < 0.0001. f ¹³C labeling pattern of TCA cycle intermediates following labeling with U-¹³C-glucose (left) or ¹³C₅,¹⁵N₂-glutamine (right). Bar plots show the relative intensity of stable isotope enrichment fractions of TCA cycle intermediates for parental and VEN-RE MOLM-13 cells. The glucose-derived ¹³C enrichment fraction (total of M + 2, +3, and +4) for fumarate (relative to succinate enrichment levels) shows slightly decreased levels in VEN-RE cells. Cit Citrate, Suc Succinate, Fum Fumarate, Mal Malate. g Results of Seahorse assays showing OCR in parental (dotted lines) and VEN-RE (solid lines) MOLM-13 cells treated with indicated inhibitors for 1 h. h Results of Seahorse assays showing OCR in VEN-RE MOLM-13 cells transfected with shCON (dotted lines) or shMCL-1 (solid lines) that were induced with or without doxycycline (100 ng/mL) for 6 h