New Target in an Old Enemy: Herbicide (R)-Dichlorprop Induces Ferroptosis-like Death in Plants

Iron is an essential microelement in plants that is involved in several growth processes. The use of herbicides may cause the abnormal aggregation of iron in leaves, but the regulatory mechanisms underlying this phenomenon remain unclear. Here, we show that chiral herbicide (R)-dichlorprop ((R)-DCPP) triggers ferroptosis-like death in Arabidopsis thaliana. (R)-DCPP led to reactive oxygen species (ROS) accumulation and iron aggregation, and these processes were iron dependent. Under (R)-DCPP treatment, ROS, lipid hydrogen peroxides, and malondialdehyde were significantly accumulated. In addition, (R)-DCPP induced the depletion of glutathione, ascorbic acid, and glutathione peroxidase as well as the accumulation of toxic lipid peroxides. Thus, oxidation imbalance led to cell death, and this mode of action could be inhibited by the ferroptosis inhibitor ferrostatin-1 or ciclopirox olamine. NADPH oxidases were found to be involved in herbicide-induced ROS accumulation, and lipoxygenase and NADPH cytochrome P450 oxidase were shown to positively regulate (R)-DCPP-induced lipid peroxidation. Overall, these results indicate that the iron- and ROS-dependent signaling cascades were involved in the (R)-DCPP-induced phytotoxicity pathway, which disrupted the structure of plant cell membranes and triggered ferroptosis. Generally, this study provides new insight into the mechanisms of pesticide phytotoxicity and suggests new therapeutic directions to protect nontarget plants.