Fine particulate matter induces mitochondrial dysfunction and oxidative stress in human SH-SY5Y cells

Exposure to ambient fine particulate matter (PM_2.5) is associated with neurodegenerative diseases. Mitochondrion is key to brain degeneration. However, the underlying mechanism of PM_2.5-induced brain injury, especially mitochondrial damage, is still unclear. In this study, changes in mitochondrial dynamics, mitochondrial permeability transition pore (mPTP), mitochondrial DNA (mtDNA) and oxidative stress in human SH-SY5Y cells exposed to PM_2.5 at different concentrations (0, 25, 100, and 250 μg mL^-1) were investigated. The results showed that PM_2.5 caused more mitochondrial swell, accompanied by the opening of mPTP and the decrease of ATP levels, mitochondrial membrane potential and mtDNA copy number in SH-SY5Y cells. PM_2.5 significantly enhanced the expression of mitochondrial fission/fusion genes (Drp1 and OPA1) and affected the gene expression of CypD, SIRT3, and COX Ⅳ in SH-SY5Y cells. Besides, PM_2.5 triggered the increase of cellular ROS, Ca²⁺ and Aβ-42 levels, inhibition of manganese-superoxide dismutase (SOD₂) activities, reduction of GSH levels GSH/GSSG ratio, and elevation of mitochondrial malondialdehyde contents. It suggests that mitochondrial dysfunction and oxidative stress are the potential mechanisms underlying PM_2.5-induced brain nerve cell injury, which may be related to neurological diseases. Additionally, our study elucidated that PM_2.5 components trigger different cytotoxicity.