Eccentric and Concentric Cycling Induces Rapid Sex-Specific Differences in the Expression of Mitochondrial Proteins in COPD Skeletal Muscle

Exercise can have a positive therapeutic effect in people with chronic obstructive pulmonary disease (COPD), where skeletal muscle dysfunction is strongly associated with poor prognosis. However, the precise effect of exercise on skeletal muscle mitochondrial biology in COPD is not yet understood. COPD is an inflammatory lung condition that is characterised by obstructed airflow from the lungs. Around 390 million people are affected across the globe, with exposure to environmental tobacco smoke being the greatest risk factor. While it is described as a chronic disease, complications can lead to acute respiratory failure. Different types of physical exercise may have a potential therapeutic benefit, but COPD often limits such activities in affected people. Here we explored the effect that a session of eccentric or concentric cycling can induce in the proteome of mitochondria isolated from skeletal muscle of COPD individuals. We report changes in the abundance of proteins that have been associated with mitochondrial ultrastructure and morphology, with some sex-specific changes, while others are common to both male and female participants. We found that the changes in protein expression are distinct between the different types of cycling exercise and that there are more proteins with significantly altered abundance in response to both types of exercise, in males. Rapid, exercise specific changes in the skeletal muscle mitochondrial proteome clearly demonstrate that treatment strategies for this common and debilitating condition should be managed differently in males and females. Immediate proteomic changes have not been measured previously and could be interpreted as a more ‘reflexive’ effect of exercise, least moderated by background heterogeneity. Our data show that all exercise types probably do not elicit the same quality of therapeutic benefit and therefore should be evaluated carefully before recommendation to people with COPD.