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. 2025 Aug;241(8):e70079.
doi: 10.1111/apha.70079.

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

Aldjia Abdellaoui  1   2 , Farés Gouzi  3 , Cécile Notarnicola  1 , Annick Bourret  1 , Amandine Suc  3 , Dalila Laoudj-Chenivesse  1 , Nelly Héraud  2 , Jacques Mercier  3 , Christian Préfaut  3 , Maurice Hayot  3 , Pascal Pomiès  1
Affiliations

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

Aldjia Abdellaoui et al. Acta Physiol (Oxf). 2025 Aug.

Abstract

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.

Keywords: COPD; exercise; mitochondrial dysfunction; muscle; oxidative stress; pulmonary rehabilitation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Respiration rates. Analysis of maximal respiration rates in the presence of (A) palmitoyl‐carnitine (V max PC ), (B) pyruvate (V max Pyr ), (C) rotenone and succinate (V Rot‐Succ ), (D) antimycin A and TMPD and ascorbate (V Ant‐TMPD + Asc ), (E) oligomycin (V Oligo ), and (F) ATP synthesis rate (V ATP ) and (G) ATP synthesis rate/Oxygen consumption ratio (ATP/O) in muscle mitochondria from sedentary healthy subjects (SHS) and patients with COPD (COPD), before (Pre‐Ex) and after (Post‐Ex) exercise training. Lines link muscle mitochondria from the same subject, and the means are indicated. p‐values of group effect, exercise effect, and interaction (Exercise × Group) are indicated. Repeated measures two‐way ANOVA was used. (*), (†) and (‡) indicate statistical significance at p < 0.05, p < 0.01, and p < 0.001, respectively, and (ns) indicates statistically nonsignificant.
FIGURE 2
FIGURE 2
Mitochondrial complexes. Analysis of the expression levels of mitochondrial (A) Complex I, (B) Complex II, (C) Complex III, (D) Complex IV, and (E) Complex V in muscle mitochondria from sedentary healthy subjects (SHS) and patients with COPD (COPD), before (Pre‐Ex) and after (Post‐Ex) exercise training. Lines link muscle mitochondria from the same subject, and the means are indicated. a.u. = arbitrary unit. p‐values of group effect, exercise effect, and interaction (Exercise × Group) are indicated. Repeated‐measure two‐way ANOVA was used. (*) indicates statistical significance at p < 0.05, and (ns) indicates statistically nonsignificant.
FIGURE 3
FIGURE 3
Mitochondrial oxidative stress, biogenesis, and dynamics. Analysis of the levels of (A) lipid peroxidation, (B) protein carbonylation, (C) Mn‐SOD expression, (D) PGC‐1α expression, (E) NRF1 expression, (F) TFAM expression, and (G) MFN2/DRP1 ratio in muscle mitochondria from sedentary healthy subjects (SHS) and patients with COPD (COPD), before (Pre‐Ex) and after (Post‐Ex) exercise training. Lines link muscle mitochondria from the same subject, and the means are indicated. a.u. = arbitrary unit. p‐values of Group effect, Exercise effect, and Interaction (Exercise × Group) are indicated. Repeated‐measure two‐way ANOVA was used. (*), (†), and (‡) indicate statistical significance at p < 0.05, p < 0.01, and p < 0.001, respectively, and (ns) indicates statistically nonsignificant.
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References

    1. Henrot P., Dupin I., Schilfarth P., et al., “Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting,” International Journal of Molecular Sciences 24, no. 7 (2023): 6454. - PMC - PubMed
    1. Gifford J. R., Trinity J. D., Layec G., et al., “Quadriceps Exercise Intolerance in Patients With Chronic Obstructive Pulmonary Disease: The Potential Role of Altered Skeletal Muscle Mitochondrial Respiration,” Journal of Applied Physiology 119, no. 8 (2015): 882–888. - PMC - PubMed
    1. Meyer A., Zoll J., Charles A. L., et al., “Skeletal Muscle Mitochondrial Dysfunction During Chronic Obstructive Pulmonary Disease: Central Actor and Therapeutic Target,” Experimental Physiology 98, no. 6 (2013): 1063–1078. - PubMed
    1. Puente‐Maestu L., Pérez‐Parra J., Godoy R., et al., “Abnormal Mitochondrial Function in Locomotor and Respiratory Muscles of COPD Patients,” European Respiratory Journal 33, no. 5 (2009): 1045–1052. - PubMed
    1. Naimi A. I., Bourbeau J., Perrault H., et al., “Altered Mitochondrial Regulation in Quadriceps Muscles of Patients With COPD,” Clinical Physiology and Functional Imaging 31, no. 2 (2011): 124–131. - PubMed

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