Molecular mechanism of mitochondrial dysfunction modulating the relationship between chronic liver disease. Increasing electron transport chain (ETC) leads to excess reactive oxygen species (ROS), causing corresponding metabolic changes and ultimately ETC dysfunction. Alcohol metabolism, which decreases GSH levels in mitochondria, increases ROS production and causes iron death. Interfering with autophagy by silencing Parkin led to enhanced apoptotic signaling, while SIRT3 increased BNIP3 expression in hepatocytes via the ERK-cAMP pathway, promoting BNIP3-mediated mitochondrial autophagy. Mitochondrial injury can lead to mtDNA leakage, which triggers an inflammatory response through the cGAS-String pathway. cGAS-STRING signaling pathway key molecules, cGAS, STING, and IRF3 expression levels, as well as the downstream NF-κB nuclear translocation, were significantly increased, and at the same time, it caused the accumulation of TDP-43 in the mitochondria of hepatocytes, which induced mitochondrial damage. Inflammatory response significantly increased the expression levels of NLRP3, caspasel and IL-1β in the liver, resulting in iron accumulation and lipid accumulation. ETC: Electron transport chain; ROS: Reactive oxygen species
