Effect of ambient PM_2.5 on lung mitochondrial damage and fusion/fission gene expression in rats

Exposure to ambient fine particulate matter (PM_2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM_2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM_2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM_2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM_2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM_2.5; (2) PM_2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM_2.5 inhibited Mn superoxide dismutase (MnSOD), Na⁺K⁺-ATPase, and Ca²⁺-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM_2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM_2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM_2.5 induces lung injury, contributing to respiratory diseases.