Hydroxytyrosol influences exercise-induced mitochondrial respiratory complex assembly into supercomplexes in rats

Hydroxytyrosol (HT) has been demonstrated to improve mitochondrial function, both in sedentary and in exercised animals. Herein, we assessed the effects of two different doses of HT on exercise-induced mitochondrial respiratory complex (C) assembly into supercomplexes (SCs) and the relation of the potential results to OPA1 levels and oxidative stress. Wistar rats were allocated into six groups: sedentary (SED), sedentary consuming 20 mg/kg/d of HT (SED-20), sedentary consuming 300 mg/kg/d of HT (SED-300); exercised (EXE), exercised consuming 20 mg/kg/d of HT (EXE-20) and exercised consuming 300 mg/kg/d of HT (EXE-300). Animals were exercised and/or supplemented for 10 weeks, and assembly of SCs, mitochondrial oxidative status and expression of OPA1 were quantified in the gastrocnemius muscle. Both EXE and EXE-20 animals exhibited increased assembly of CI into SCs, but this effect was absent in EXE-300 animals. Levels of CIII2 assembled into SCs were only increased in EXE-20 animals. Notably EXE-300 animals showed a decreased relative expression of s-OPA1 isoforms. Therefore, HT exerted dose-dependent effects on SC assembly in exercised animals. Although the mechanisms leading to SCs assembly in response to exercise and HT are unclear, it seems that a high HT dose can prevent SCs assembly during exercise by decreasing the expression of the s-OPA1 isoforms. [Display omitted] •The mitochondrial respiratory complexes can be assembled into supercomplexes thereby improving mitochondrial function.•Hydroxytyrosol (HT) modulates supercomplexes assembly in exercised animals.•A high HT dose can prevent exercise-induced SCs assembly because it down-regulate the expression of the short OPA1 isoforms.•Low HT dose might be a potential pharmacological approach in order to prevent mitochondrial-related diseases.•Low HT dose might help to elevate aerobic ATP supply within contracting skeletal muscle.