Figure 6.

Venetoclax enhances mitochondrial metabolism via NF-κB activation in NK cells

(A) Correlation between the NF-κB activation signature and OXPHOS signature in venetoclax-treated or untreated C3 NK cells.

(B) OCR kinetics in C3 NK cells treated with 400 nM venetoclax, 25 μg/mL SN50 (a cell-permeable inhibitor of NF-κB translocation) or venetoclax plus SN50 or left untreated.

(C–F) Quantification of basal OCR (C), maximal OCR (D), spare respiratory capacity (E), and ATP production rate (F) derived from (B), n = 9, biological replicates.

(G) Confocal microscopy images (left) showing MitoTracker Green and MitoTracker Red CMXRos staining in C3 NK cells treated with 25 μg/mL SN50, 400 nM venetoclax, or venetoclax plus SN50 or left untreated. The graphs (right) show the corresponding quantification of the mean fluorescence intensity (one data point per cell). Results from two independent experiments as presented.

(H) Correlation between the NF-κB activation signature and OXPHOS signature in venetoclax-treated or untreated total NK cells.

(I) Confocal microscopy images (left) and statistical analysis (right) illustrating MitoTracker Green and MitoTracker Red CMXRos staining in total NK cells treated with 25 μg/mL SN50, 400 nM venetoclax, or venetoclax plus SN50 or left untreated. The results represent two independent experiments.

Statistical significance was determined by one-way ANOVA with Tukey’s multiple comparisons test (C–G and I) and hypergeometric test (A and H). Data are presented as mean ± SD. For (B), data are presented as mean ± SEM.