Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease
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RESEARCH
Open Access
Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease Gulam Haji1,2†, Coen H. Wiegman1*† , Charalambos Michaeloudes1, Mehul S. Patel2, Katrina Curtis2, Pankaj Bhavsar1, Michael I. Polkey2, Ian M. Adcock1, Kian Fan Chung1,2 and on behalf of the COPDMAP consortium
Abstract Background: Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD. Methods: Bronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/ 4 for measurement of mitochondrial function. Results: Decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression. Conclusions: Mitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs. Keywords: COPD, Airways, Quadriceps, Oxidative stress, Mitochondria
* Correspondence: [email protected] † Gulam Haji and Coen H. Wiegman contributed equally to this work. 1 Airways Disease, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the artic
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