Human Sirtuin 3 (SIRT3) Protein

Background

SIRT3 is a NAD+-dependent deacetylase primarily localized in the mitochondria, where it plays a critical role in regulating mitochondrial metabolism, energy production, and oxidative stress response SIRT3 deacetylates and activates key mitochondrial enzymes, including acetyl-CoA synthetase 2 (ACSS2), superoxide dismutase 2 (SOD2), and components of the electron transport chain, enhancing ATP production, fatty acid oxidation, and antioxidant defense SIRT3 is essential for maintaining mitochondrial homeostasis during energy stress, such as fasting or caloric restriction, by stimulating pathways that improve energy efficiency and reduce reactive oxygen species (ROS) levels SIRT3 also promotes cellular survival under oxidative stress by deacetylating SOD2, which neutralizes superoxide radicals Dysregulation of SIRT3 is associated with aging, metabolic disorders, cardiovascular disease, and neurodegeneration, where impaired mitochondrial function leads to cellular damage and energy deficiency SIRT3 has tumor suppressor properties as it inhibits aerobic glycolysis (Warburg effect) in cancer cells by regulating key metabolic enzymes Its activation is being explored as a therapeutic strategy to combat mitochondrial dysfunction, improve metabolic health, and delay aging-related diseases