Fig. 4: Isofalcarintriol (IFT) impairs mitochondrial respiration in cells, C. elegans and mice.

a Seahorse XF Cell Mito Stress Assay showing the OCR development over time after injection of isofalcarintriol (1a) (10 µM) and positive controls in HepG2 cells (DMSO n = 12; IFT n = 11 independent cell samples per condition). Quantification of respiration parameters in a, including (b) a decrease of respiration (IFT: p < 0.0001) (c) ATP production (calculated) (IFT: p = 0.001) and (d) maximal respiration. e Seahorse XF Cell Mito Stress Assay showing the OCR development over time after overnight pre-treatment with isofalcarintriol (1a) (10 µM) and positive controls in HepG2 cells. n = 12 independent cell samples per condition. Quantification of respiration parameters in (e), including (f) basal respiration (IFT: p = 0.0003), (g) ATP production (calculated) (IFT: p < 0.0001) and (h) maximum respiration (IFT: p = 0.016). i Seahorse XF Cell Mito Stress Assay showing the OCR development over time after overnight pre-treatment of isofalcarintriol (1a) (1 nM, 10 nM) in C. elegans (DMSO and IFT 1 nM: n = 7; IFT 10 nM: n = 5 biologically independent samples per condition. Quantification of respiration parameters, including (j) basal respiration (IFT 10 nM: p = 0.038) and (k) maximal respiration. l Indirect calorimetry of female C57BL/6NRj mice (DMSO: n = 10; IFT: n = 11 mice) on chow diet, and quantification of OCR upon treatment with isofalcarintriol (1a) (0.1 mg/kg body weight) (p = 0.031). Data are represented as average ± SD, + SD or ± SEM (l), and (b)–(d), (f)–(h), and (j)–(k) were measured in ≥ 3 independent experiments. Statistics: one-way ANOVA with or without Dunnett’s or Bonferroni’s post-hoc test. Source data are provided as a Source Data file.