Aflatoxin B1 induces ROS‐dependent mitophagy by modulating the PINK1/Parkin pathway in HepG2 cells

Abstract

AbstractAflatoxin B1 (AFB1) is extremely harmful to both humans and animals. Mitophagy is a selective process of self‐elimination and has an important role in controlling mitochondrial quality. The present study aimed to investigate the effect of reactive oxygen species (ROS) accumulation on AFB1‐induced mitophagy in HepG2 cells to provide a new perspective from which to design novel therapeutic strategies to treat AFB1 poisoning. ROS release was induced in HepG2 cells with AFB1 (10 μmol/L). Cell autophagy activity, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) levels, Parkin translocation and both the transcription and expression of mitophagy‐related proteins were measured when N‐acetyl‐L‐cysteine (NAC) partially decreased the ROS level, while the knockdown of nuclear factor erythroid 2‐related factor 2 (Nrf2) resulted in a large accumulation of ROS. The results reveal that NAC pretreatment ameliorated the decline in both the MMP and the ATP levels while also activating phosphoglycerate mutase 5 (PGAM5)‐PTEN‐induced kinase 1 (PINK1)/Parkin, while the Nrf2 knockdown group exhibited the opposite trend. These results suggest that AFB1‐induced mitophagy in HepG2 cells depends on ROS, and proper ROS activates mitophagy to play a protective role.