Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice

• Published in: Communications biology 2021-07, Vol.4 (1), p.894-894, Article 894
• Main Authors: Wang, Lixiang, Li, Xin, Hanada, Yuki, Hasuzawa, Nao, Moriyama, Yoshinori, Nomura, Masatoshi, Yamamoto, Ken
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/31; 13/51; 14/1; 14/19; 14/63; 38/61; 631/250/256; 631/80/39/2348; Biology; Biomedical and Life Sciences; Cytokines; DNA damage; Dynamin; Endoplasmic reticulum; Hepatocytes; Immune response; Inflammasomes; Inflammation; Life Sciences; Lipopolysaccharides; Liver cancer; Liver diseases; Macrophages; Mitochondria; Phenotypes; Protein deficiency; Proteins
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02413-6

Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1 LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1 -knockout ( Drp1 LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo. Wang et al. report that deficiency of dynamin-related protein 1, which controls mitochondrial fission, accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice. Thus, they highlight mitochondria dynamics dysfunction as a new mechanism of liver disease development.