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

Area of Science:

• Mitochondrial biology
• Exercise physiology
• Nutritional biochemistry

Background:

• Hydroxytyrosol (HT) is known to improve mitochondrial function in both sedentary and exercised states.
• Exercise promotes the assembly of mitochondrial respiratory chain complexes into supercomplexes (SCs).
• The role of HT dosage on exercise-induced SC assembly and its underlying mechanisms remains to be fully elucidated.

Purpose of the Study:

• To investigate the dose-dependent effects of HT on exercise-induced mitochondrial respiratory complex (C) assembly into supercomplexes (SCs).
• To explore the relationship between HT supplementation, SC assembly, OPA1 levels, and oxidative stress in exercised rats.
• To determine if high doses of HT might interfere with exercise-induced mitochondrial adaptations.

Main Methods:

• Wistar rats were divided into six groups: sedentary (SED) and exercised (EXE), with subgroups receiving either 20 mg/kg/d or 300 mg/kg/d of HT for 10 weeks.
• Mitochondrial respiratory complex (C) assembly into supercomplexes (SCs) was quantified in the gastrocnemius muscle.
• Mitochondrial oxidative status and the expression of OPA1 (Optic Atrophy 1) were assessed.

Main Results:

• Exercise alone and low-dose HT (20 mg/kg/d) with exercise increased the assembly of Complex I (CI) into SCs.
• High-dose HT (300 mg/kg/d) with exercise did not enhance CI assembly into SCs.
• Complex III (CIII)2 assembly into SCs was elevated only in the low-dose HT exercise group (EXE-20).
• The high-dose HT exercise group (EXE-300) exhibited decreased relative expression of short-form OPA1 (s-OPA1) isoforms.

Conclusions:

• Hydroxytyrosol (HT) exerts dose-dependent effects on exercise-induced mitochondrial supercomplex assembly.
• Low-dose HT appears to support exercise-induced mitochondrial adaptations, while high-dose HT may impede them.
• High-dose HT might inhibit SC assembly during exercise, potentially by reducing s-OPA1 isoform expression.