Restoring the function of damaged mitochondria is a novel strategy for treating COPD

Published Online: March 28, 2015

Inflammation and the formation of free radicals (oxidative stress) are important processes in the lungs of patients with chronic obstructive pulmonary disease (COPD), as these symptoms can lead to airway constriction and emphysema. Mitochondria are the cell’s powerhouses and also produce large amounts of oxidative stress. In a recent study published in The Journal of Allergy and Clinical Immunology (JACI), C. Wiegman and colleagues demonstrate a defect in mitochondrial function in human airway smooth muscle cells which was also found in lung tissue from ozone exposed mice—and which is linked to the enhanced oxidative stress seen in COPD. However, the mitochondrial-directed antioxidant MitoQ was able to reverse the defective mitochondrial function and restore “normal” airway smooth muscle function and prevent ozone-induced airway hyperresponsiveness and inflammation.

The authors of this study isolated airway smooth muscle cells and biopsies from non-smoker and smoker volunteers, and COPD patients. Mitochondrial function was compared at baseline and after exposure of smooth muscle cells to hydrogen peroxide, to induce oxidative stress. Treatment with the mitochondrial-directed antioxidant MitoQ had a protective effect on mitochondria and prevented exaggerated cell proliferation and inflammation. In a mouse model of oxidative stress induced by chronic exposure to ozone that mimics several important processes that are seen in the lungs of COPD patients, prophylactic treatment with MitoQ restored mitochondrial function in lung tissue, prevented airway hyper-responsiveness to acetylcholine, and prevented the presence of inflammatory cells and mediators.

The results of this study show that there is a defect in mitochondrial function in human airway smooth muscle cells from COPD patients and in the lungs of the mice that have been exposed to chronic oxidative stress, and that this defect prevents the normal protective cellular response to exogenous stress. This mitochondrial dysfunction was induced by oxidative stress and reversed by the mitochondrial-directed antioxidant MitoQ. This study indicates that treatments that target mitochondria-derived oxidative stress represent a promising new therapeutic strategy in COPD. Drugs such as metformin, used to treat diabetes, have this property, and clinical trials in COPD are currently being undertaken and may provide further evidence for the importance of acquired mitochondrial defects in the pathobiology of COPD.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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