Nrf2 protects against diverse PM2.5 components-induced mitochondrial oxidative damage in lung cells

Nrf2 is an important transcription factor implicated in the oxidative stress response, which has been reported to play an important role in the way by which air pollution particulate matter (PM2.5) induces adverse health effects. This study investigates the mechanism by which Nrf2 exerts its protective effect in PM2.5 induced toxicity in lung cells. Lung cells silenced for Nrf2 (shNrf2) demonstrated diverse susceptibility to various PM extracts; water extracts containing high levels of dissolved metals exhibited higher capacity to generate mitochondrial reactive oxygen species (ROS) and hence increased oxidative stress levels. Organic extracts containing high levels of polycyclic aromatic hydrocarbons (PAHs) increased mortality and reduced ROS production in the silenced cells. shNrf2 cells exhibited a higher basal mitochondrial respiration rate compared to the control cells. Following exposure to water extracts, the mitochondrial respiration increased, which was not observed with the organic extracts. shNrf2 cells exposed to the organic extracts showed lower mitochondrial membrane potential and lower mtDNA copy number. Nrf2 may act as a signaling mediator for the mitochondria function following PM2.5 exposure. [Display omitted] •Nrf2 has a crucial role in PM2.5 induced toxicity.•PAHs and metals possess different toxicity mechanisms.•Nrf2 affects the mitochondrial membrane potential.•Metals from PM2.5 may act as uncouplers.