Journal of Translational Medicine (Oct 2023)

Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions

  • Melissa Myint,
  • Francesca Oppedisano,
  • Valeria De Giorgi,
  • Byeong-Moo Kim,
  • Francesco M. Marincola,
  • Harvey J. Alter,
  • Salvatore Nesci

DOI
https://doi.org/10.1186/s12967-023-04627-0
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 16

Abstract

Read online

Abstract Liver steatosis, inflammation, and variable degrees of fibrosis are the pathological manifestations of nonalcoholic steatohepatitis (NASH), an aggressive presentation of the most prevalent chronic liver disease in the Western world known as nonalcoholic fatty liver (NAFL). Mitochondrial hepatocyte dysfunction is a primary event that triggers inflammation, affecting Kupffer and hepatic stellate cell behaviour. Here, we consider the role of impaired mitochondrial function caused by lipotoxicity during oxidative stress in hepatocytes. Dysfunction in oxidative phosphorylation and mitochondrial ROS production cause the release of damage-associated molecular patterns from dying hepatocytes, leading to activation of innate immunity and trans-differentiation of hepatic stellate cells, thereby driving fibrosis in NASH.

Keywords