Genetic disruption of mitochondrial dynamics and stasis leads to liver injury and tumorigenesis.

ABSTRACT: Mitochondrial fission is mediated by dynamin-related protein 1 (gene name DNM1L) and fusion by mitofusins (MFN1 and MFN2) and optic atrophy 1. The role of mitochondrial dynamics in liver disease and cancer remains poorly understood. We analyzed single, double, and triple liver-specific KO mice lacking mitochondrial fission and fusion proteins using systematic analyses of mitochondrial morphology, untargeted metabolomics, RNA-seq, hydrodynamic tail vein injection of oncogenes, and human hepatocellular carcinoma samples. Liver-specific Dnm1l-KO (L-Dnm1l-KO) mice showed increased alanine aminotransferase levels and hepatic fibrosis, with spontaneous liver tumors developing by 12 to 18 months of age. L-Mfn1- and L-Mfn2-KO mice showed no significant liver damage or tumor development, although a

SUBMITTER: Ma X 

PROVIDER: S-EPMC12904713 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature