The mitochondrial phenotype of peripheral muscle in chronic obstructive pulmonary disease: disuse or dysfunction?
BACKGROUND
Peripheral muscle alterations have been recognized to contribute to disability in chronic obstructive pulmonary disease (COPD).


OBJECTIVE
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.


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. H(2)O(2) production per mitochondrion was higher both under basal and ADP-stimulated states, suggesting that mitochondria from COPD muscle have properties that potentiate H(2)O(2) release. Direct assessment of mitochondrial sensitivity to Ca(2+)-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 H(2)O(2) and more resistant to PTP opening. These results thus argue against the presence of pathological mitochondrial alterations in this category of patients with COPD.
Picard
Martin
M
Department of Kinesiology and Physical Education, McGill University, Montreal, PQ, Canada.
Godin
Richard
R
Sinnreich
Michael
M
Baril
Jacinthe
J
Bourbeau
Jean
J
Perrault
Hélène
H
Taivassalo
Tanja
T
Burelle
Yan
Y