National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Royal Brompton Hospital, Guy's and St. Thomas' NHS Trust, London, United Kingdom.
Am J Respir Cell Mol Biol. 2022 Oct;67(4):471-481. doi: 10.1165/rcmb.2022-0041OC.
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.
线粒体功能障碍已在慢性阻塞性肺疾病（COPD）中报道。间充质干细胞向气道平滑肌细胞（ASMCs）转移线粒体可以减轻氧化应激诱导的线粒体损伤。目前尚不清楚这种线粒体转移是否会发生在肺部的结构细胞之间，以及它在调节健康和 COPD 气道中的生物能量和细胞功能方面可能发挥什么作用。在这里，我们发现来自健康戒烟者和 COPD 患者的 ASMC 可以交换线粒体，这个过程至少部分是通过细胞外囊泡发生的。暴露于香烟烟雾会导致线粒体功能障碍，并导致 ASMC 捐赠更多的线粒体，这表明后者可能是一种应激反应机制。接受线粒体的健康戒烟者 ASMC 表现出线粒体生物发生和呼吸增加，细胞增殖减少，无论线粒体是来自健康戒烟者还是 COPD ASMC。我们的数据表明，结构细胞之间的线粒体转移是调节气道内生物能量和细胞功能的一种动态平衡机制，可能代表着一种内在机制，可以逆转 COPD 等疾病中线粒体功能障碍的功能后果。
