Fig. 4: SQR inhibition via Qp site SDHC-mutant introduction sensitizes MM to venetoclax.

a SQR, b SDH and c CS activities were determined in KMS11 and L363, SDHCKO cells expressing SDHC-WT or SDHC-R72C mutant constructs. n = 4 independent experiments except L363 SQR and SDH activity (n = 3). Data are presented as mean values ± SEM. Adjusted p values are calculated using a two-way ANOVA with post-hoc Sidak’s multiple comparisons test. d SDHC-WT and SDHC-R72C mutant-expressing cells ± 0.5 μM venetoclax (24 h) were evaluated for viability by AnnexinV/DAPI flow cytometric staining, demonstrating increased sensitivity of SDHC-R72C cells to venetoclax. n = 4 independent experiments. Adjusted p values are calculated using a two-way ANOVA with post-hoc Tukey’s multiple comparisons test. e Spare respiratory capacity determined in the indicated SDHC-WT and SDHC-R72C-mutant-expressing cells demonstrated a net reduction in SRC upon introduction of the mutant. n = 6 replicate Seahorse wells except KMS11 SDHC-R72C (n = 4). Data are presented as mean values ± SEM. Adjusted p values are calculated using a two-way ANOVA with post-hoc Sidak’s multiple comparisons test. **** denotes p value < 0.0001. Source data are provided as a source data file.