Because patients with
chronic obstructive pulmonary disease (
COPD) are often physically inactive, it is still unclear whether the lower respiratory capacity in the locomotor muscles of these patients is due to cigarette smoking per se or is secondary to physical deconditioning. Accordingly, the purpose of this study was to examine mitochondrial alterations in the quadriceps muscle of 10 mice exposed to 8 mo of cigarette
smoke, a sedentary mouse model of
emphysema, and 9 control mice, using immunoblotting, spectrophotometry, and high-resolution respirometry in permeabilized muscle fibers. Mice exposed to
smoke displayed a twofold increase in the oxidative stress marker, 4-HNE, (P < 0.05) compared with control mice. This was accompanied by significant decrease in
protein expression of UCP3 (65%), ANT (58%), and mitochondrial complexes II-V (∼60%-75%). In contrast, maximal
ADP-stimulated respiration with complex I and II substrates (CON: 23.6 ± 6.6 and SMO: 19.2 ± 8.2 ρM·mg-1·s-1) or
octanoylcarnitine (CON: 21.8 ± 9.0 and SMO: 16.5 ± 6.6 ρM·mg-1·s-1) measured in permeabilized muscle fibers, as well as
citrate synthase activity, were not significantly different between groups. Collectively, our findings revealed that sedentary mice exposed to cigarette
smoke for 8 mo, which is typically associated with
pulmonary inflammation and
emphysema, exhibited a preserved mitochondrial respiratory capacity for various substrates, including
fatty acid, in the skeletal muscle. However, the mitochondrial adaptations induced by cigarette
smoke favored the development of chronic oxidative stress, which can indirectly contribute to augment the susceptibility to muscle fatigue and exercise intolerance.NEW & NOTEWORTHY It is unclear whether the exercise intolerance and skeletal muscle
mitochondrial dysfunction observed in patients with
COPD is due to cigarette
smoke exposure, per se, or if they are secondary consequences to inactivity. Herein, while long-term exposure to cigarette
smoke induces oxidative stress and an altered skeletal muscle phenotype, cigarette
smoke does not directly contribute to
mitochondrial dysfunction. With this evidence, we demonstrate the critical role of physical inactivity in cigarette
smoke-related skeletal muscle dysfunction.