Mitochondrial Dysfunction and Defects in Mitochondrial Adaptation to Exercise Training in the Muscle of Patients With COPD : Disease Versus Disuse

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AIM: Chronic obstructive pulmonary disease (COPD) is frequently associated with skeletal muscle dysfunction, having a considerable impact on exercise tolerance and patient prognosis. Mitochondria play a role in skeletal muscle weakness and exercise intolerance in COPD, but the majority of studies on mitochondrial function are biased by the fact that physical activity is greater in healthy subjects than in patients. Furthermore, exercise training (ET) has been proposed as a therapeutic strategy to prevent skeletal muscle dysfunction in COPD, but very few results are available on mitochondrial adaptation in response to ET. METHODS: Skeletal muscle mitochondrial function and the potential efficacy of ET on this function were compared between 12 patients with COPD and 21 healthy subjects with similar low levels of physical activity. Various markers of mitochondrial respiration, oxidative stress, biogenesis, and dynamics were assessed. RESULTS: Lower oxidative phosphorylation (OxPhos; p < 0.001) and increased nonphosphorylating respiration (p = 0.025) and mitochondrial oxidative damage (lipid peroxidation (p = 0.014) and protein carbonylation (p = 0.020)) were observed in patients. While ET increased OxPhos efficiency (p = 0.011) and reduced nonphosphorylating respiration (p < 0.001) and lipid peroxidation (p < 0.001) in patients' muscle mitochondria, it fails to improve maximal respiration (p = 0.835) and expression of the antioxidant enzyme MnSOD (p = 0.606), mitochondrial transcription factor TFAM (p = 0.246), and mitochondrial complexes I, III, and IV (p = 0.816, p = 0.664, p = 0.888, respectively) as observed in healthy subjects. CONCLUSION: The mitochondrial dysfunction and the defects in mitochondrial adaptation to ET that we observe in the muscle of patients with COPD are intrinsic to the disease and do not arise from muscle disuse.

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