Abstract
Diquat (DQ), a contact herbicide extensively utilized in both agricultural and nonagricultural domains, exhibits a high correlation with neuronal disorders. Nevertheless, the toxicity and underlying mechanisms associated with exposure to environmental concentrations of DQ remain ambiguous. Here, we report dose-dependent cellular neurotoxicity of DQ in Caenorhabditis elegans. First, DQ significantly compromised the development and brood size of worms, shortened the lifespan, and caused epidermal abnormalities. An unbiased transcriptomic analysis disclosed several pathways related to cell death and peroxisome homeostasis underlying this organismal-level toxicity. Moreover, exposure of DQ to C. elegans led to a notable increase of embryonic cell death. Concurrently, DQ exposure specifically caused the loss of dopamine neurons but not two other types of neurons in adulthood, which is in accordance with DQ-induced muscle-related defects such as pharyngeal pumping, body bends, and head thrashes. Mechanistically, DQ exposure induces the generation of reactive oxygen species (ROS) and enhances glutathione-related ROS scavenging pathway. Protein levels and activities of mitochondrial electron transport chain complexes were specifically impaired in the DQ-treated worms. Collectively, this study suggests an ROS-mediated cell death pathway involving the neuronal and behavioral toxicity of DQ, which offers a novel mitochondria-related perspective to elucidate the general toxicity caused by a widely distributed herbicide, DQ, at near-environment concentrations.