Mitofusin 2 is required for preventing deoxynivalenol-induced porcine intestinal epithelial cell damage.

BACKGROUNDS: Deoxynivalenol (DON) is an abundant environmental pollutant in feed, posing serious health hazards to animals. However, whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood. Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs. METHODS: Firstly, two groups of weaning pigs were fed a basal diet, or basal diet supplemented with 4 mg DON/kg for 3 weeks. Additionally, another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline. In addition, the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line (IPEC-1) by overexpressed plasmids of dynamin related protein 1 (Drp1) and mitofusin 2 (Mfn2) which were determined by animal studies. Finally, a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage. RESULTS: Dietary DON caused jejunal damage and inflammation, reduced intestinal Drp1, mitofusin 1 (Mfn1) and Mfn2, and induced cell apoptosis. DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2, and increased cell apoptosis. Moreover, DON challenge also resulted in cell damage and mitochondrial dysfunction, accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells. Subsequently, Mfn2, but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression, suppressed cell apoptosis, mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge. Finally, M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis, rescued mitochondrial dysfunction, barrier function impairment and cell damage. CONCLUSIONS: Overall, our study demonstrates that DON exposure triggers Mfn2 protein dysregulation, which in turn mediates DON-induced intestinal epithelial damage in piglets.