Fig. 5: Lactate production supports OXPHOS by tailoring NAD+-to-NADH balance.
a–c, OCR measurement (a), the average of basal OCR (b) and SRC (c) in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and LDHA gRNAs (LDHA sgRNA-1 and sgRNA-2) stimulated with either Ctrl or FGK45 mAb under glucose-deplete media following the additions of oligomycin, FCCP, Rot/AA and 2-deoxyglucose (2-DG). d,e, The ratios of TMRM to MG (d) and the ratios of NAD+ to NADH (e) in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and LDHA gRNAs (LDHA sgRNA-1 and sgRNA-2) stimulated with either Ctrl or FGK45 mAb under glucose-deplete media. f,g, The real-time change of OCR (f, left), the average of basal OCR (f, right) and SRC (g) in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and LDHA gRNAs (LDHA sgRNA-1 and sgRNA-2) stimulated with either control vehicle (Ctrl) or FGK45 mAb in the absence or presence of NR under glucose-deplete media. h, The real-time change of ECAR (left) and the average of basal ECAR (right) in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and LDHA gRNAs (LDHA sgRNA-1 and sgRNA-2) stimulated with either control vehicle (Ctrl) or FGK45 mAb in the absence or presence of NR under glucose-deplete media. i, qPCR analysis of mRNA expression of pro-inflammatory marker genes in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and LDHA gRNA (LDHA sgRNA) stimulated with or without FGK45 in the absence or presence of NR. Data are representative of three individual experiments with n = 3 per group in a–c and f–h and n = 3 per group in d, e and i. All data are the mean ± s.d. and analyzed by a two-tailed Student’s t-test.
