The role of Drp1 – Pink1 – Parkin – mediated mitophagy in perfluorobutane sulfonate– induced hepatocyte damage

Abstract

Perfluorobutane sulfonate (PFBS) is recognized as a highly persistent environmental contaminant, notorious for its chemical stability and enduring presence in ecosystems. Its propensity for persistence and environmental mobility allows PFBS to infiltrate the human body, predominantly accumulating in the liver where it poses a potential risk for hepatic damage. This investigation aimed to explore the outcomes of PFBS on the physiological functionalities of hepatocytes in vitro. To this end, hepatocytes were exposed to 750 ug/ml PFBS, followed by an analysis of various cellular phenotypes and functionalities, including assessments of cell viability and mitochondrial integrity. The findings indicated that PFBS exposure led to a suppression of cell proliferation and an increase in apoptotic cell death. Moreover, PFBS exposure was found to augment the generation of reactive oxygen species (ROS) and induce significant mitochondrial dysfunction. Gene expression analysis identified significant changes in genes associated with numerous tumor signaling pathways and autophagy signaling pathways. Further examinations revealed an increase in cellular mitophagy following PFBS exposure, coupled with the activation of the mitophagy-associated Drp1/Pink1/Parkin pathway. Inhibition of mitophagy was observed to concurrently amplify cellular damage and inhibit the Drp1/Pink1/Parkin pathway. Together, these findings highlight PFBS’s capacity to inflict hepatocyte injury through mitochondrial disruption, positioning Drp1/Pink1/Parkin-mediated mitophagy as a crucial cellular defense mechanism against PFBS-induced toxicity.