Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

中文翻译：

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重新审视慢性阻塞性肺疾病的气道上皮功能障碍和机制：线粒体损伤的作用

长期暴露于环境危害会导致气道上皮功能障碍，主要是物理屏障受损、免疫功能障碍以及修复或再生。气道上皮功能受损随后导致气道炎症和重塑加剧，这是慢性阻塞性肺病（COPD）的主要特征。线粒体损伤已被认为是COPD气道异常的机制之一，与气道炎症和气流受限密切相关。在这篇综述中，我们评估了 COPD 气道上皮线粒体损伤的最新证据，并重点关注线粒体损伤在气道上皮功能障碍中的作用。此外，详细讨论了线粒体损伤介导的气道上皮功能障碍的可能机制，并总结了近期与气道上皮靶向线粒体治疗相关的策略。结果表明，线粒体质量和氧化应激的失调可能导致 COPD 患者气道上皮功能障碍。这可能是由于作为介导细胞代谢异常的中央细胞器的线粒体损伤造成的。线粒体损伤介导线粒体活性氧引起的促细胞衰老效应，有效加剧不同类型的程序性细胞死亡，参与脂质代谢异常，最终促进气道上皮功能障碍并引发COPD气道异常。这些可以通过针对线粒体损伤因子和线粒体转移来预防。因此，由于线粒体损伤作为气道上皮细胞稳态失衡的核心因素参与 COPD 进展，因此它可能是恢复 COPD 气道上皮完整性和功能的治疗干预的新靶点。