The mechanism of mitochondrial damage in chronic obstructive pulmonary disease induced by cigarette smoke and its therapeutic implications.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by persistent and progressive airflow limitation. Cigarette smoking is recognized as the primary risk factor. There is emerging evidence that mitochondrial dysfunction is a key pathological mechanism in smoking-induced COPD. Reactive oxygen species and other toxic components found in tobacco smoke can directly damage mitochondrial DNA, impair the function of the electron transport chain, decrease ATP production, and promote the excessive generation of reactive oxygen species, resulting in a self-perpetuating cycle of oxidative damage. Furthermore, disturbances in mitochondrial dynamics, including imbalances in fusion and fission processes, defective mitophagy, and heightened oxidative stress, contribute to increased airway epithelial cell apoptosis, persistent inflammatory responses, and impaired tissue repair. Mitochondria-derived damage-associated molecular patterns (DAMPs) have also been shown to activate the NLRP3 inflammasome, exacerbating pulmonary inflammation. Targeting mitochondrial dysfunction represents a promising therapeutic avenue for the prevention and treatment of COPD. Accordingly, this review summarized recent advances in understanding the role of tobacco-induced mitochondrial damage in COPD pathogenesis and highlighted its potential as a novel intervention target.