Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage

Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson's disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 mu M PQ concentrations, and autophagy pathways were activated at a concentration of 100 mu M in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 mu M PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson's disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Long-term exposure to paraquat may increase the risk of Parkinson's disease, with ROS-mediated mitochondrial fission contributing to excessive mitophagy, which can be significantly ameliorated by mdivi-1.