Transferrin confers imidacloprid resistance by attenuating ROS-induced apoptotic signaling in the white-backed planthopper, Sogatella furcifera.

Transferrins constitute a multifunctional protein family involved in cellular iron homeostasis, reproductive regulation, and innate immune responses. Recently, the critical roles of these proteins in insect pesticide resistance have garnered considerable attention. However, the molecular mechanisms by which transferrins alleviate pesticide-induced toxicity remain poorly understood. In this study, we performed genome-wide identification of transferrin family members in Sogatella furcifera (white-backed planthopper, WBPH), a devastating agricultural pest, and investigated their functional roles in imidacloprid resistance. Our analysis identified three novel transferrin proteins and confirmed SfTsf1 as the sole iron-binding protein among them. Through integrated biochemical assays and RNAi-mediated gene silencing, we demonstrated that SfTsf1 enhanced imidacloprid resistance in WBPH by preventing cellular iron overload and suppressing subsequent reactive oxygen species (ROS) generation. Using complementary approaches including RNA-seq, RNA knockdown, and TUNEL assays, we revealed that imidacloprid induced WBPH mortality through apoptotic cell death, and SfTsf1 could attenuate pesticide-induced apoptosis by modulating mitochondrial-mediated apoptotic pathways. These findings provide novel mechanistic insights into transferrin-mediated pesticide tolerance in insects and highlight transferrins as promising targets for developing innovative pest management strategies.