Mitochondrial Influence on Performance Fatigability: Considering Sex Variability

ABSTRACT Objective Existing literature indicates that females generally demonstrate higher fatigue resistance than males during isometric contractions. However, when it comes to single-limb dynamic exercises, the intricate interplay between performance fatigability (PF), cardiovascular responses, and muscle metabolism in relation to sex differences remains underexplored. Purpose This study investigates how sex affects the relationship between muscle oxidative characteristics and the development of PF during dynamic single-leg exercise. Methods Twenty-four young healthy participants (12 males vs 12 females) performed a constant-load single-leg knee extension task (85% peak power output; 60 rpm) to exhaustion (TTE). Neuromuscular assessments via transcranial magnetic and peripheral stimulations were conducted before and after exercise to evaluate central and peripheral factors of PF. Vastus lateralis muscle biopsies were obtained for mitochondrial respiration and immunohistochemistry analyses. Results Participants performed similar total work (28 ± 7 vs 27 ± 14 kJ, P = 0.81) and TTE (371 ± 139 vs 377 ± 158 s, P = 0.98); after the TTE, females’ maximal isometric voluntary contraction (MVIC: −36% ± 13% vs −24% ± 9%, P = 0.006) and resting twitch (RT; −65% ± 9% vs −40% ± 24%, P = 0.004) force declined less. No differences were observed in supraspinal neuromuscular factors ( P > 0.05). During exercise, the cardiovascular responses differed between sexes. Although fiber type composition was similar (type I: 47% ± 13% vs 56% ± 14%, P = 0.11), males had lower mitochondrial net oxidative capacity (61 ± 30 vs 89 ± 37, P = 0.049) and higher Complex II contribution to maximal respiration (CII; 59% ± 8% vs 48% ± 6%, P < 0.001), which correlated with the decline in MVIC ( r = −0.74, P < 0.001) and RT ( r = −0.60, P = 0.002). Conclusions Females display greater resistance to PF during dynamic contractions, likely due to their superior mitochondrial efficiency and lower dependence on mitochondrial CII activity.