Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease

Gulam Haji,Ian M Adcock,Coen H Wiegman,Kian Fan Chung,Michael I Polkey,Mehul S Patel,Charalambos Michaeloudes,Katrina Curtis,Pankaj Bhavsar

doi:10.1186/s12931-020-01527-5

Abstract

BackgroundMitochondrial 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.MethodsBronchial 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.ResultsDecreased 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.ConclusionsMitochondrial 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.

Highlights

Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD)
reactive oxygen species (ROS) and electron transport chain (ETC) complex protein levels Patients with Global initiative for chronic Obstructive Lung Disease (GOLD) Grade 2 COPD demonstrated a significant reduction in airway mitochondrial membrane potential (ΔΨm) when compared to ex-smokers (p < 0.01) or never-smokers (p < 0.05) (Fig. 1a), with higher
In the patients with COPD, concomitant examination of mitochondrial dysfunction of the quadriceps muscle obtained from the same subjects at GOLD Grade 2, we found no evidence of mitochondrial dysfunction with respect to Mitochondrial membrane potential (ΔΨm)

Summary

Introduction

Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). Patients with more advanced COPD experience frequent exacerbations caused by viruses and/or bacteria, associated with a faster decline in lung function and greater mortality [1, 2]. Oxidative stress derived both exogenously through cigarette smoking and endogenously through inflammatory processes is an important mechanism driving the damage and inflammation in COPD [1]. Mitochondrial reactive oxygen species (mtROS) are maintained as a balance between production and scavenging processes from the antioxidant defence system. Elevated levels of mtROS can initiate processes that influence mitochondrial function and integrity

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