PINK1/Parkin-mediated mitophagy was activated against 1,4-Benzoquinone-induced apoptosis in HL-60 cells

Hematotoxicity of benzene is derived mainly from its active metabolite, 1,4-Benzoquinone (1,4-BQ), which induces cell apoptosis and mitochondrial damage. Damaged mitochondria are degraded through a specialized autophagy pathway, called mitophagy, which is driven by PINK1/Parkin signaling. However, whether mitophagy is involved in 1,4-BQ-induced toxicity remains unclear. This study was designed to investigate whether PINK1/Parkin-mediated mitophagy is activated in 1,4-BQ-treated HL-60 cells, and the roles mitophagy plays in 1,4-BQ-induced apoptosis. Our results demonstrated that 1,4-BQ induced autophagy in HL-60 cells, characterized by increased LC3-II/LC3-I ratio and Beclin1 expression, as well as decreased expression of p62. We confirmed the presence of mitophagosomes using electron microscopy, and found that 1,4-BQ-induced autophagy was blocked by pretreatment with the mitophagy inhibitor Cyclosporine A (CsA). In addition, we found that 1,4-BQ induced mitochondrial stress through decreased mitochondrial membrane potential (MMP) and increasedproduction of reactive oxygen species (ROS). We also confirmed that 1,4-BQ-induced mitophagy was mediated by the PINK1/Parkin pathway, illustrated by increased expression of PINK1 and Parkin mRNA and protein. Finally, we examined 1,4-BQ-induced apoptosis with or without CsA, which demonstrated that apoptosis increased after mitophagy inhibition, suggesting that mitophagy has a protective effect in this context. In conclusion, this study demonstrates that the activated PINK1/Parkin-mediated mitophagy exerts a significantly protective effect against 1,4-BQ-induced apoptosis in HL-60 cells. [Display omitted] A proposed model of molecular iteraction to delineate the actin mechanisms of 1,4-benzoquinone in HL60 cell. 1,4-benzoquinone, a metabolite of benzene, decreases mitochondrial membrane potential (MMP), increases in reactive oxygen species (ROS), and activates the PINK1/Parkin pathway mitophagy that plays a protective role in apoptosis. •1,4-BQ, the active metabolite of benzene, induced autophagy in vitro.•1,4-BQ induced PINK1/Parkin-mediated mitophagy was first proposed.•ROS plays an important role in 1,4-BQ-induced PINK1/Parkin pathway mitophagy.•Mitophagy plays a protective effect against 1,4-BQ induced cell apoptosis.