Mitochondrial Transfer Regulates Bioenergetics in Healthy and Chronic Obstructive Pulmonary Disease Airway Smooth Muscle

Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress–induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.

Correspondence and requests for reprints should be addressed to Pankaj K. Bhavsar, Ph.D., Airway Disease, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail:
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Supported by Sanming Project of Medicine in Shenzhen grant SZSM201612096 and the British Heart Foundation, Imperial College Centre for Translational and Experimental Medicine, Studentships.

Author Contributions: J.F.G., C.M., and P.K.B. conceived experiments and wrote the manuscript. P.K.B., T.R., C.M., K.F.C., C.K.M.H., and B.X. secured funding. J.F.G. performed experiments. K.F.C., T.R., J.C.W.M., A.J.H., and A.V.R. provided expertise and feedback.

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Originally Published in Press as DOI: 10.1165/rcmb.2022-0041OC on June 28, 2022

Author disclosures are available with the text of this article at www.atsjournals.org.

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