Ferroptosis-like cell death associated with Vibrio parahaemolyticus infection in the clam Meretrix petechialis.

Abstract

Vibrio parahaemolyticus is a major pathogen causing disease outbreaks in marine bivalves, but the mode of cell death induced by infection in clams remains unclear. In this study, we investigated whether V. parahaemolyticus infection triggers ferroptosis-like cell death in the clam Meretrix petechialis. Transmission electron microscopy revealed marked mitochondrial ultrastructural alterations in hepatopancreas tissues, including mitochondrial shrinkage and cristae disruption in infected clams. Vibrio infection also induced Fe2+ accumulation in hemocytes, while reactive oxygen species (ROS) levels and lipid peroxidation were significantly increased in hepatopancreas tissues. Meanwhile, reduced glutathione (GSH) levels and MpGPX4 expression were significantly decreased, indicating impairment of the GSH-GPX4 antioxidant axis. The mRNA expression of ferroptosis-related genes was also significantly altered, with upregulation of MpACSL4, MpSAT1, and MpFerroportin, and downregulation of MpGCL, MpNrf2, and MpFerritin. In addition, Torin 1 treatment reduced hemocyte viability and decreased MpGPX4 expression, suggesting a possible association between mTOR-related signaling and MpGPX4 expression. Lipidomic analysis further showed that Ferrostatin-1 reshaped infection-associated lipid metabolism, particularly phospholipid remodeling and PUFA-related pathways, including glycerophospholipid, linoleic acid, and arachidonic acid metabolism. Collectively, our study integrates a Vibrio infection model, Ferrostatin-1 intervention and mTOR-GPX4-related analysis to provide a multi-level evidence framework for ferroptosis-like responses during V. parahaemolyticus infection in M. petechialis, offering new insights into pathogen-induced cell death mechanisms in marine bivalves.