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The Mitochondrial Phenotype of Peripheral Muscle in Chronic Obstructive Pulmonary Disease

Disuse or Dysfunction?

¹ Department of Kinesiology and Physical Education, McGill University, ² Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, ³ Neuromuscular Research Group, Montreal Neurological Institute, and ⁴ Département de Kinésiologie, Université de Montréal, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Tanja Taivassalo, Ph.D., Assistant Professor and FRSQ Research Scholar, Department of Kinesiology and Physical Education, 475 Pine Avenue West, Room 222, McGill University, Montreal, PQ H2W 1S4, Canada. E-mail: tanja.taivassalo{at}mcgill.ca

Rationale: Peripheral muscle alterations have been recognized to contribute to disability in chronic obstructive pulmonary disease (COPD).

Objectives: To describe the mitochondrial phenotype in a moderate to severe COPD population and age-matched controls.

Methods: Three primary aspects of mitochondrial function were assessed in permeabilized locomotor muscle fibers.

Measurements and Main Results: Respiration rates per milligram of fiber weight were significantly lower in COPD muscle compared with healthy age-matched control muscle under various respiratory states. However, when variations in mitochondrial volume were taken into account by normalizing respiration per unit of citrate synthase activity, differences between the two groups were abolished, suggesting the absence of specific mitochondrial respiratory impairment in COPD. H₂O₂ production per mitochondrion was higher both under basal and ADP-stimulated states, suggesting that mitochondria from COPD muscle have properties that potentiate H₂O₂ release. Direct assessment of mitochondrial sensitivity to Ca²⁺-induced opening of the permeability transition pore (PTP) indicated that mitochondria from patients with COPD were more resistant to PTP opening than their counterparts in control subjects.

Conclusions: Comparison of these results with those of studies comparing healthy glycolytic with oxidative muscle suggests that these differences may be attributable to greater type II fiber expression in COPD muscle, as mitochondria within this fiber type have respiratory function similar to that of mitochondria from type I fibers, and yet are intrinsically prone to greater release of H₂O₂ and more resistant to PTP opening. These results thus argue against the presence of pathological mitochondrial alterations in this category of patients with COPD.

Key Words: chronic obstructive pulmonary disease • skeletal muscle • mitochondrial function • oxidative stress • permeability transition pore

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject It is presently unclear whether the abnormal locomotor muscle condition in patients with chronic obstructive pulmonary disease (COPD) is a result of specific muscle dysfunction or the result of prolonged disuse. What This Study Adds to the Field This study presents evidence demonstrating that the mitochondrial phenotype of patients with moderate to severe COPD is normal, thereby disproving a specific mitochondrial dysfunction hypothesis in this population.

 

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