Fig. 4: Dnmt3a^R878H/+ HSPCs have greater uptake and accumulation of long-chain alkyl-TPP molecules.

A Chemical structures of TPP⁺ derivatives MitoQ, d-TPP, h-TPP and m-TPP. Created in BioRender: https://BioRender.com/j69r060. B Quantification of puromycin incorporation in control and Dnmt3a^R878H/+ HSCs treated with vehicle control (DMSO), MitoQ, d-TPP, h-TPP, or m-TPP. Bars represent mean ± SEM, points from biological replicate mice (n = 7 Control DMSO, n = 6 R878H/ + DMSO, n = 5 Control MitoQ, n = 6 R878H/+ MitoQ, n = 5 Control d-TPP, n = 6 R878H/+ d-TPP, n = 3 Control h-TPP, n = 3 R878H/+ h-TPP, n = 3 Control m-TPP, n = 3 R878H/+ m-TPP). Statistical analysis used two-way ANOVA with Dunnett’s multiple comparisons test. C Experimental design (left) and OCR plot (right) used to quantify (D), basal and maximal respiration (left) and spare respiratory capacity (right) in d-TPP treated control and Dnmt3a^R878H/+ HSPCs. E Quantification of d-TPP induced ECAR in d-TPP treated control and Dnmt3a^R878H/+ HSPCs. F Proton-leak driven respiration in d-TPP treated control and Dnmt3a^R878H/+ HSPCs. D–F Bars represent mean ± SEM, points are from biological replicate mice (n = 4). Statistical analyses used two-way ANOVA with Sidak’s multiple comparisons test (D, left), one-way ANOVA with Tukey’s multiple comparisons test (D, right, F), and unpaired, two-tailed t test (E). G Experimental design. H Ratio of MitoQ in the mitochondria vs. cytoplasm of control and Dnmt3a^R878H/+ HSPCs. Bars represent mean ± SEM, points from biological replicate mice (n = 4). Statistical analysis used ratio paired, two-tailed t test. Source data are provided as a Source Data file.