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

The invasive golden apple snail, <i>Pomacea canaliculate</i>, 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 <i>squalene monooxygenase</i>, <i>lanosterol synthase</i>, and cholesterol catabolic enzymes (<i>CYP3A24</i>, <i>CYP2U1</i>). Concurrently, sphingolipid metabolism exhibited dual perturbation, with both sphingomyelin accumulation and ceramide elevation mediated by differential expression of <i>DEGS2</i> and <i>MOXD1</i>. 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.