Mitochondrial dysfunction: A promising therapeutic target for liver diseases.

ABSTRACT

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy, which is mainly produced by the mitochondria. Liver tissues of patients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mitochondrial lesions, mitochondrial DNA damage, disturbed mitochondrial dynamics, and compromised ATP production. Overproduction of mitochondrial reactive oxygen species induces oxidative damage to mitochondrial proteins and mitochondrial DNA, decreases mitochondrial membrane potential, triggers hepatocyte inflammation, and promotes programmed cell death, all of which impair liver function. Mitochondrial DNA may be a potential novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus. We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases, such as hepatocellular carcinoma, viral hepatitis, drug-induced liver injury, alcoholic liver disease, and non-alcoholic fatty liver disease. This review also discusses mitochondrion-centric therapies for treating liver diseases.