Mitochondrial dysfunction and mitophagy pathway activation in hepatitis E virus-infected livers of Mongolian gerbils

Recently, hepatitis E virus (HEV) has caused large outbreaks and presented a significant public health problem. Thus, the mechanism of HEV has attracted increasing research attention. Previous studies revealed that HEV infection induced hepatocyte injuries and structural and functional changes in mitochondria. These pathological changes affected the life cycle of hepatocytes. However, the precise underlying mechanism and the effector protein responsible for this process remain unclear. In the present study, mitochondrial function and the expression of mitophagy-associated mRNA transcripts and proteins were detected in an HEV- infected Mongolian gerbil model. Observation of ultrastructural changes in the liver of the inoculated group revealed the disappearance of mitochondrial cristae of mitochondrion, blurring of the bilayer structure and cavitation in the cytoplasm. The results showed that the mitochondrial transmembrane potential of decreased, mitochondrial transition pore (MPTP) opening increased, reactive oxygen species (ROS) production increased, and glutathione peroxidase (GSH-Px) activity decreased in the HEV-inoculated group. Moreover, the LC3, Beclin1, BNIP3L, Parkin, PINK1 and P62 mRNA levels were significantly increased (p < 0.05 and p < 0.01) in the inoculated group. Western blot and immunohistochemistry assay analyses detected the upregulation of the mitophagy-associated proteins LC3, Beclin1, BNIP3L, Parkin, PINK1 and P62 (p < 0.05 and p < 0.01) in HEV-infected gerbils. All these data demonstrated that HEV infection in vivo induced mitochondrial dysfunction and the activation of the mitophagy pathway, which might be one of the key factors in hepatocyte injury.