Fig. 5: Glucose flux regulates mitochondrial motility and remodels crista structure through hexosamine pathway in OXPHOSLO LUSC.
From: Spatial mapping of mitochondrial networks and bioenergetics in lung cancer
Data are mean ± s.e.m. (n = 3 biological replicates), unpaired two-tailed t-test unless specified otherwise. a, Diagram of proposed model that glucose flux regulates the remodelling of mitochondrial cristae and reduction of OXPHOS function through hexosamine pathway. b–e, Basal mitochondrial displacement in human LUAD (H1975 and A549) and SCC (RH2 and Tu686) cells (b) and vehicle (Veh)- or treatment-driven mitochondrial displacement in RH2 cells (c–e). RH2 cells were treated with KL-11743 at indicated concentrations for 72 h (c), low-glucose (5.5 mM) and galactose medium for 24 h (d), or the hexosamine pathway inhibitors azaserine (0.5 μM) and OSM1 (25 μM) for 72 h (e). n = 150 per cell line or per treatment condition. One-way ANOVA, Dunnett test (c). f, Western blots of RH2 cells treated with indicated concentrations of KL-11743 for 72 h probed with indicated antibodies. g, Mitochondrial displacement in RH2 and H1975 cells treated with Ctrl siRNA (siCtrl) and OGT siRNA (siOGT) for 72 h. n = 150 per treatment condition. h, Percentage of type I, II and III cristae in RH2 cells treated with indicated concentrations of KL-11743. n > 1,500 mitochondria. One-way ANOVA, Dunnett test. i, Mitochondrial maximal OCR in RH2 cells treated with indicated concentrations of KL-11743 for 72 h. One-way ANOVA, Dunnett test. j,k, [18F]FBnTP uptake (j) and complex I and II MRC (k) of subcutaneous xenografts of human LUSC (RH2) cells treated with vehicle or KL-11743 (100 mg kg−1, 10 days). (j) n = 22 tumours for Veh; n = 29 tumours for KL-11743.
