Theasaponin E1 Induce Ferroptotic Cell Death in Pomacea canaliculata through Coordinated Disruption of Cholesterol Homeostasis and Sphingolipid Metabolism

The invasive golden apple snail, Pomacea canaliculate, threatens agriculture and public health globally. This study systematically investigates the molluscicidal mechanism of theasaponin E1 (TSE1), a tea saponin monomer. TSE1 exhibited concentration- and time-dependent toxicity. Transcriptomics revealed dysregulation of cholesterol homeostasis, including marked upregulation of squalene monooxygenase, lanosterol synthase, and cholesterol catabolic enzymes (CYP3A24, CYP2U1). Concurrently, sphingolipid metabolism exhibited dual perturbation, with both sphingomyelin accumulation and ceramide elevation mediated by differential expression of DEGS2 and MOXD1. Ultrastructural analysis showed mitochondrial cristae dissolution and membrane rupture, with ferroptosis activation through voltage-dependent anion channel 2 upregulation and oxidative stress. Notably, granulocytes displayed distinct resistance to TSE1-induced cytotoxicity, suggesting cell-type specific protective mechanisms. These findings establish that TSE1 exerts its molluscicidal effect through coordinated disruption of lipid homeostasis, culminating in iron-dependent cell death. The conserved ferroptotic pathway and cell-selective vulnerabilities identified in this study provide critical insights for developing targeted, environmentally sustainable molluscicides.