Uranium triggers ferroptosis-like cell death in Vicia faba roots by increasing iron accumulation and inhibiting glutathione peroxidase activity

Abstract

Uranium (U) is a non-essential and toxic element that can cause cell death in plants, but the mechanism is unclear. In the present study, we found that U triggered iron (Fe)- and reactive oxygen species (ROS)-dependent ferroptosis-like cell death in Vicia faba roots. The results showed that U entered V. faba root cells and even accumulated in the nucleus and organelles. U accumulation resulted in obvious changes in mitochondrial morphology, including shrunken shape, rupture of outer membrane, increased density of inner membrane and fuzzy crista. Compared with the control, the accumulation of Fe and ROS in V. faba roots increased after U exposure, while the peroxidase (POD) and glutathion peroxidase (GPX) activities decreased significantly, which was only 57.7% and 14.3% of control, respectively. Transcriptomic data showed that the expression of genes related to ROS production was mainly up-regulated (e.g. NDH , CCR , RbohB ), while the expression of genes related to ROS scavenging was mainly down-regulated (e.g. GPX4 , POD1 , POD7 ). These results led to excessive accumulation of ROS in root cells and triggered ferroptosis-like cell death. The key mechanism of U triggering ferroptosis-like cell death was to increase Fe accumulation and decrease GPX activity, so the cell death was promoted by addition of Fe (FeSO 4 and FeCl 3 ), and was inhibited by the lipophilic antioxidants [ferrostatin (Fer-1) and Vitamin E (VE)] and the Fe chelators [ciclopirox olamine (CPX)]. In conclusion, we demonstrated for the first time that U triggered ferroptosis-like cell death in V. faba roots. Our results provide a new insight for revealing the toxicological mechanism of U and other heavy metals in plants. • Uranium triggered ferroptosis-like cell death in Vicia faba roots. • Uranium accumulated in the nucleus and organelles after entering root cells. • Uranium induced iron accumulation and lipid peroxidation in Vicia faba roots. • Uranium severely inhibited GPX4 expression and glutathione peroxidase activity.