NAD-dependent protein deacetylase sirtuin 3, mitochondrial (SIRT3)

NAD-dependent protein deacetylase sirtuin 3, mitochondrial (SIRT3) is the primary protein deacetylase located within the mitochondrial matrix, where it serves as a master regulator of metabolic homeostasis [UniProt: Q9NTG7]. It utilizes NAD+ as a co-substrate to remove acetyl groups from various metabolic enzymes, thereby coordinating the tricarboxylic acid (TCA) cycle, fatty acid oxidation, and the urea cycle in response to cellular energy demands [PMID: 21167305]. A critical function of SIRT3 is the regulation of mitochondrial oxidative stress; by deacetylating and activating superoxide dismutase 2 (SOD2), it facilitates the scavenging of reactive oxygen species and protects the cell from oxidative damage [PMID: 21126506]. In human pathology, reduced SIRT3 activity is linked to the development of metabolic syndrome, cardiac hypertrophy, and neurodegenerative conditions like Alzheimer's disease [PMID: 23603399]. Conversely, its role in cancer is dualistic, acting as a tumor suppressor by maintaining genomic stability or as a survival factor for certain established tumors. Therapeutic interest focuses on SIRT3 activators, such as honokiol, to treat age-related metabolic and cardiovascular diseases, while selective inhibitors like 3-TYP are primarily used as research tools to investigate its complex biological roles [PMID: 25605930, PMID: 24513116].

Other names

Sirtuin 3SIR2L3SIR2-like protein 3Mitochondrial sirtuinRegulatory protein SIR2 homolog 3

SIRT3 functions as an NAD+-dependent deacetylase that removes acetyl groups from lysine residues of mitochondrial proteins, thereby modulating their enzymatic activity and metabolic flux [PMID: 21167305]. It also exhibits mono-ADP-ribosyltransferase activity. By activating antioxidant enzymes such as superoxide dismutase 2 (SOD2) through deacetylation at K122, SIRT3 reduces mitochondrial reactive oxygen species (ROS) levels [PMID: 21126506].