Elevated Mitochondrial Oxidative Stress Blunts Skeletal Muscle Adaptations to Endurance Exercise

Reactive oxygen species (ROS) are implicated in the regulation of numerous cellular processes including tissue repair, cell cycle dynamics and mitochondrial biogenesis. ROS have been shown to increase during muscle contractions, however details concerning their cellular origin and the specific species produced have not been not fully clarified. A coincident rise in ATP demand during contractions make ETC-derived superoxide a likely source of exercise-induced ROS, however the chronic consequences of this form of cellular stress have not been evaluated. PURPOSE: To determine the mitochondrial effects of endurance exercise training in mice possessing normal and impaired abilities to metabolize the mitochondrial superoxide radical. METHODS: Six-month-old mice containing normal (MnSOD+/+) or decreased (MnSOD+/-) levels of MnSOD underwent four months of progressive endurance exercise (MnSOD+/+EX, N=10; MnSOD+/- EX, N=8) or remained sedentary (MnSOD+/+SED, N=10; MnSOD+/- SED, N=8). At 10 months of age, mice were tested for maximum aerobic capacity and sacrificed 1 week later. Markers of mitochondrial content and function were assessed within the tibialis anterior muscle. RESULTS: Maximal exercise performance (total distance run) was greater in MnSOD+/+EX vs. MnSOD+/+SED (439±39 vs. 306±24 meters, P0.05). Maximum oxygen consumption and cytochrome c oxidase (COX) protein content was higher in EX vs. SED within each genotype (VO2max, MnSOD+/+ and MnSOD+/- greater by 12 and 13%, respectively, P<0.05; COX protein, MnSOD+/+ and MnSOD+/- higher by 46 and 39%, respectively, P<0.05). CONCLUSIONS: Greater levels of mitochondrial superoxide result in an attenuation of maximal aerobic energy provision following exercise training, likely due to oxidative damage to mitochondrial enzymes. This work was supported by a grant from the Canadian Institutes of Health Research.