SIRT3: A potential therapeutic target for liver fibrosis

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis. (c) 2024 Elsevier Inc. All rights reserved.