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FB1 causes barrier damage to vascular endothelial cells through ferroptosis by a PINK1/Parkin mediated mitophagy-dependent mechanism

Year: 2025

Type: article

Abstract: Fumonisin B1 (FB1) is an environmental mycotoxin produced mainly by fungi of the genus Fusarium . Exposure to FB1 can lead to pulmonary edema in pigs, likely caused by damage to vascular endothelial cells, but the mechanism of FB1-induced damage was unknown. Here, we found that FB1 damages vascular endothelial cells through ferroptosis, marked by iron-dependent membrane lipid peroxidation, and through mitophagy, a selective autophagy that targets mitochondria. FB1 exposure reduced barrier-related gene expression and increased pro-inflammatory factors. Ferroptosis was evidenced by elevated iron, ROS, lipid peroxidation, and ferroptotic markers (TFR, ACSL4), alongside decreased GSH, SLC7A11, and GPX-4 levels in vascular endothelial cells. Importantly, the ferroptosis inhibitor, Ferrostatin-1, reversed the vascular endothelial cells’ barrier damage, inflammation, and ferroptosis caused by FB1. FB1-induced mitophagy was demonstrated by detecting decreased mitochondrial membrane potential and increased levels of mitophagy-related proteins. Surprisingly, silencing PINK1 using siRNA not only diminished mitophagy, cellular damage, and inflammatory responses induced by FB1, but also mitigated FB1-induced ferroptosis. In conclusion, this study demonstrates that FB1 causes vascular endothelial cell damage by ferroptosis in a mitophagy-dependent manner. This study thus lays a mechanistic foundation for the study of FB1 causing pulmonary edema in pigs and for exploring options for therapeutic intervention in conditions caused by this mycotoxin, which causes substantial harm to both human and animal health. • 1、 FB1 causes both barrier damage and inflammation in SUVEC cells. • 2、 FB1 caused lipid peroxidation, iron accumulation and ferroptosis in SUVEC cells. • 3、 FB1 causes excessive mitophagy in SUVEC cells. • 4、 Inhibiting ferroptosis alleviated the barrier damage of SUVEC cells caused by FB1. • 5、 Inhibiting mitophagy alleviated ferroptosis induced by FB1 in SUVEC cells.

Source: Chemico-Biological Interactions