Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells

Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases. [Display omitted] •FPM inhibits A549 cell growth, induces G1/S cell cycle arrest and promotes EMT.•FPM blocks autophagic flux and disturbs redox balance in A549 cells.•FPM upregulates DRP1 and disarranges mitochondrial homeostasis in A549 cells.•JNK activation mediated redox imbalance underlies FPM’s impacts in A549 cells.