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Mitochondrial DNA in liver inflammation and oxidative stress
- Zhang, Xufei, Wu, Xiuwen, Hu, Qiongyuan, Wu, Jie, Wang, Gefei, Hong, Zhiwu, Ren, Jianan
- Life sciences 2019
- Hepatitis B virus, Toll-like receptor 9, adenosine triphosphate, biosynthesis, genes, hepatocytes, hepatoma, inflammasomes, inflammation, interferons, liver, mitochondria, mitochondrial DNA, oxidative phosphorylation, oxidative stress, polypeptides
- The function of liver is highly dependent on mitochondria producing ATP for biosynthetic and detoxifying properties. Accumulating evidence indicates that most hepatic disorders are characterized by profound mitochondrial dysfunction. Mitochondrial dysfunction not only exhibits mitochondrial DNA (mtDNA) damage and depletion, but also releases mtDNA. mtDNA is a closed circular molecule encoding 13 of the polypeptides of the oxidative phosphorylation system. Extensive mtDNA lesions could exacerbate mitochondrial oxidative stress and subsequently cause damage to hepatocytes. When mtDNA leaves the confines of mitochondria to the cytosolic and extracellular environment, it can act as damage-associated molecular patterns (DAMPs) to trigger the inflammatory response through the Toll-like receptor 9, inflammasomes, and stimulator of interferon genes (STING) pathways and further exacerbate hepatocellular damage and even remote organs injury. In addition, mtDNA also plays a vital role in hepatitis B virus (HBV)-related liver injury and hepatocellular carcinoma (HCC). In this review, we describe mtDNA alterations during liver injury, focusing on the mechanisms of mtDNA-mediated liver inflammation and oxidative stress injury.