Translational machinery of mitochondrial mRNA is promoted by physical activity in Western diet-induced obese mice.

ABSTRACT

AIM: Mitochondria-encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. Our purpose was to determine whether Western diet (WD)-induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype. METHODS: Obesity was induced with 8-wk WD feeding, and in the final 4 wks, half of mice were allowed VWR. Mitochondrial mRNA translation machinery including initiation factors (mtIF2/3), elongation factor Tu (TUFM) and translational activator (TACO1), and mitochondria-encoded proteins (CytB and ND4) was assessed by immunoblotting. The relation of mitochondrial mRNA translation to muscle oxidative phenotype was assessed using PGC-1α transgenic overexpression (MCK-PGC-1α vs. wild-type mice) and comparing across muscle groups in wild-type mice. RESULTS: mtIF3 and TACO1 proteins were ~45% greater in VWR than sedentary (SED), and TACO1 and mtIF2 proteins were ~60% and 125% greater in WD than normal chow (NC). TUFM protein was ~50% lower in WD-SED than NC-SED, but ~50% greater in WD-VWR compared to NC-SED. CytB and ND4 were ~40% greater in VWR and ND4 was twofold greater with WD. TUFM, TACO1, ND4 and CytB were greater in MCK-PGC-1α compared to wild-type, and mtIF2/3 contents were not different. In oxidative muscle (soleus), mitochondrial translation machinery was elevated compared to mixed (gastrocnemius) or glycolytic (extensor digitorum longus) muscles. CONCLUSION: These data suggest a novel mechanism promoting mitochondrial function by translation of mitochondrial protein following PA. This may act to promote muscle health by PA in obesity.