Fig. 5: TAZ stimulates exercise-induced mitochondrial biogenesis and increases respiratory metabolism and activity.

a Wild-type (WT) and muscle-specific TAZ knockout (mKO) mice were subjected to endurance exercise training. The gastrocnemius muscle obtained from these mice was isolated and embedded in paraffin. The sectioned tissues were immunostained with an anti-COX4 antibody to visualise the mitochondria. Scale bar = 50 μm. b Genomic DNA was isolated from the gastrocnemius muscle of mice described in (a). Relative mitochondrial DNA copy number was determined via quantitative PCR using primers for mitochondrial-encoded Cox2 and nuclear-encoded β-globin. The Ct values of mitochondrial Cox2 were normalized to those of nuclear β-globin; n = 6 for each genotype (WT untrained vs. mKO untrained; *p = 0.0188, WT untrained vs. WT trained; **p = 0.0069, WT trained vs. mKO trained; ***p = 0.0002). c Protein from the gastrocnemius muscle of mice described in (a) was assessed via immunoblotting to observe the indicated proteins. GAPDH was used as the loading control. d RNA was isolated from the gastrocnemius muscle of mice described in (a). Mitochondrial-encoded marker gene expression was analysed via quantitative reverse transcription (qRT)-PCR, n = 6 for each genotype (mt-Atp6; **p = 0.0035 for WT untrained vs. mKO untrained, **p = 0.0071 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained, mt-Co2; *p = 0.0174 for WT untrained vs. mKO untrained, ****p < 0.0001 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained, mt-Cytb; *p = 0.0214 for WT untrained vs. mKO untrained, *p = 0.0124 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained, mt-Nd5; *p = 0.0186 for WT untrained vs. mKO untrained, **p = 0.0059 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained). e Nuclear-encoded mitochondrial gene expression in the gastrocnemius muscle of mice in (a) was analysed via qRT-PCR, n = 6 for each genotype (Atp5a1; *p = 0.0137 for WT untrained vs. WT trained, **p = 0.0048 for eKO untrained vs. eKO trained, Idh3g; **p = 0.0089 for WT untrained vs. WT trained, Ndufa10; *p = 0.0205 for WT untrained vs. WT trained, Uqcrc1; ****p < 0.0001 for WT untrained vs. WT trained, **p = 0.0011 for mKO untrained vs. mKO trained). f The respiratory metabolism of mice described in (a) was analysed using the Oxylet system. Data are shown as the average values observed under light and dark conditions; n = 6 for each condition (VO₂-light; **p = 0.0033 for WT untrained vs. mKO untrained, **p = 0.0098 for WT trained vs. mKO trained, VO₂-dark; *p = 0.0146 for WT untrained vs. mKO untrained, ***p < 0.0007 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained, VCO₂-dark; ****p < 0.0001 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained, Energy expenditure-light; *p = 0.0234 for mKO untrained vs. mKO trained, Energy expenditure-dark; *p = 0.021 for WT untrained vs. mKO untrained, ***p = 0.0001 for WT untrained vs. WT trained, ****p < 0.0001 for WT trained vs. mKO trained). Ten to twelve-week-old mice were used for all panels. Data are presented as mean ± SEM for (b, d–f). Statistical significance was analysed via two-way ANOVA with Sidak’s multiple comparison test. Representative data was shown and experiments were performed at least twice with similar results for (a, c). Source data are provided as a Source data file.