The PGC-1α/SIRT3 pathway mediates the effect of DON on mitochondrial autophagy and liver injury in mice.

Abstract

Deoxynivalenol (DON)-induced liver injury is closely associated with mitochondrial dysfunction, yet it remains unclear whether this injury is mediated by mitochondrial autophagy via the PGC-1α/SIRT3 pathway. This study aimed to ascertain whether DON triggers mitochondrial autophagy, thereby causing liver injury in mice through the PGC-1α/SIRT3 pathway. Mice were orally administered DON at doses of 1.2 and 2.4 mg/kg once daily for 28 consecutive days. The results indicated that DON treatment significantly elevated the activity levels of two key liver enzymes and increased oxidative stress in the mouse liver. Additionally, DON upregulated several pivotal pro-inflammatory cytokines in the liver, leading to inflammation. The impact of DON on liver mitochondrial autophagy was assessed through histopathological analysis and observations of mitochondrial ultrastructure. These alterations were concurrent with activating the PGC-1α/SIRT3 signaling pathway in the liver following DON exposure. This research demonstrates that PGC-1α/SIRT3-regulated mitochondrial autophagy exacerbates DON-related hepatic damage, shedding light on the molecular mechanisms involved.