The mitochondrial bases of endurance exercise performance

The capacity to perform endurance exercise requires a continuous turnover of chemical energy, in the form of adenosine triphosphate (ATP), to generate force in the contracting locomotor muscles. Different energy systems facilitate the resynthesis of ATP with oxidative ATP resynthesis in the mitochondria being the primary energy system utilised during endurance exercise. Specifically, mitochondria can resynthesise ATP through oxidative phosphorylation in the process of aerobic respiration. However, whilst the mitochondria are integral to oxidative ATP turnover and endurance exercise performance, it is currently unclear whether mitochondrial content or respiration is a bigger determinant of endurance performance. Since accurately assessing exercise performance in a laboratory setting can be challenging, there is great interest in laboratory-determined physiological responses with the potential to independently correlate with or predict endurance performance in competitive settings. In this regard, maximum oxygen uptake (V̇O2max), lactate threshold, exercise economy/efficiency, V̇O2 kinetics and critical power (CP) are recognised as systemic physiological determinants of endurance performance, but the extent to which these variables relate to mitochondrial content and/or respiration is less clear. Therefore, the purpose of this thesis was to assess correlations between systemic physiological determinants of endurance performance and mitochondrial content and respiration, and how a dietary supplement with the potential to modulate mitochondrial respiration would impact exercise tolerance, which was explored across three original experimental chapters.

In the first experimental chapter, a ramp incremental cycling test was conducted to assess V̇O2peak; peak aerobic power (PAP); gas exchange threshold, as a surrogate for the lactate threshold, and V̇O2-work rate slope, as a marker of exercise economy. Skeletal muscle biopsies were attained for the assessment of citrate synthase (CS) activity, as a marker of mitochondrial content, with mitochondrial respiration assessed using high-resolution respirometry. CS activity did not significantly correlate with any of the ramp test parameters (P>0.05). However, V̇O2peak (r = 0.383, P = 0.045), PAP (r = 0.454, P = 0.015) and GET (r = 0.521, P = 0.004) were positively correlated with the respiratory phosphorylation control ratio suggesting that these ramp test parameters where typically higher in individuals with less restriction of respiration by the mitochondrial phosphorylation system.

In the second experimental chapter, the relationship between CP and V̇O2 kinetics with CS activity and mitochondrial respiratory variables were assessed. There were no significant correlations between CS activity and mitochondrial respiratory variables with CP. However, whilst not significantly correlated with mitochondrial respiratory variables, the V̇O2 slow component was inversely related to CS activity (r = -0.553, P = 0.033). Therefore, exercise economy during severe-intensity exercise appears to be positively associated with mitochondrial content.

In the final experimental chapter, the effect of six weeks dietary supplementation with ubiquinol (UQH2), which is the reduced form of Coenzyme Q10 and an integral component of the mitochondrial electron transfer system, was assessed. Compared to a placebo group UQH2 improved respiratory coupling efficiency (PLA; Pre, 0.065 ± 0.035 vs Post, 0.076 ± 0.027 and UQH2; Pre, 0.073 ± 0.038 vs Post, 0.043 ± 0.018), but did not improve exercise capacity, or estimates of the V̇O2peak and V̇O2 slow component.

The principal original observations from this thesis are: 1) positive relationships between ramp test variables and less limitation of respiration by the mitochondrial phosphorylation system; 2) inverse correlation between the V̇O2 slow component and CS activity; and 3) No improvement in exercise capacity, V̇O2peak or V̇O2 slow component after UQH2 supplementation despite improved respiratory coupling efficiency. These findings offer some original insights into the potential mitochondrial bases of endurance exercise performance.