A Potential Role for Mitochondrial DNA in the Activation of Oxidative Stress and Inflammation in Liver Disease

Abstract

Mitochondria are organelles that are essential for cellular homeostasis including energy harvesting through oxidative phosphorylation. Mitochondrial dysfunction plays a vital role in liver diseases as it produces a large amount of reactive oxygen species (ROS), in turn leading to further oxidative damage to the structure and function of mitochondria and other cellular components. More severe oxidative damage occurred in mitochondrial DNA (mtDNA) than in nuclear DNA. mtDNA dysfunction results in further oxidative damage as it participates in encoding respiratory chain polypeptides. In addition, mtDNA can leave the mitochondria and enter the cytoplasm and extracellular environment. mtDNA is derived from ancient bacteria, contains many unmethylated CpG dinucleotide repeats similar to bacterial DNA, and thus can induce inflammation to exacerbate damage to liver cells and distal organs by activating toll-like receptor 9, inflammatory bodies, and stimulator of interferon genes (STING). In this review, we focus on the mechanism by which mtDNA alterations cause liver injuries, including nonalcoholic fatty liver, alcoholic liver disease, drug-induced liver injury, viral hepatitis, and liver cancer.