Bisphenol A inhibits autophagosome-lysosome fusion and lipid droplet degradation

Abstract

Bisphenol A (BPA) is an artificial xenoestrogen widely used in consumer products containing polycarbonate plastics and epoxy resins. Exposure to BPA occurs through various channels, including ingestion of contaminated food and water. Autophagy is an important catabolic pathway that plays an important role in liver lipid metabolism. Evidence suggests that BPA exposure causes abnormal lipid droplet accumulation in liver, but the mechanism remains unknown. Here, we investigate the function of BPA in lipid metabolism and autophagy. BPA exposure increases lipid droplet and ROS accumulation which is accompanied by a defect in the fusion of the autophagosome to the lysosome. BPA exposure decreases the translocation of Stx17 to lysosome resulting in the autophagogome-lysosome fusion defect. There is no defect in the formation of the autophagosome indicated by increased LC3-II, p62 level, GFP/mRFP-LC3 ratios and decreased colocalization between LAMP2 with LC3. Mechanistically, BPA exposure reduces autophagy SNARE complex formation. Promoting autophagy by autophagy inducer (Torin2) partially reverses lipid droplet accumulation caused by BPA exposure. In summary, our results demonstrate BPA exposure inhibits autophagy resulting in decreased lipid droplet degradation and increased ROS levels. These results also provide a novel implication between autophagosome-lysosome fusion.