Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Abstract

Sirtuin 3, an NAD+-dependent deacetylase, whose expression is considered a marker in life extension, is downregulated with age and in various diseases. Sirtuin 3 is predomi- nantly localized to the mitochondria and considered a fidelity protein for the integrity and function of this organelle. Some studies report its localization in the nucleus to regulate the expression of stress response–related genes and that reduced expression of SIRT3 produces a cellular milieu permissive for human pathologies. Since the expression and activity of Sirtuin 3 are important for the regulation of antioxidant defense, metabolism, and apoptosis initiation, the expression of SIRT3 is also important in the context of age- associated illnesses. A variety of small molecules are being developed to modulate the expression or activity of Sirtuin 3 and are potentially a valuable strategy to change mitochondrial acetylome to treat several diseases. The AMPK-PGC1α-SIRT3 axis plays a critical role in preserving mitochondrial biogenesis and function. Here, we summarize how changes in Sirtuin 3 expression are regulated in cancer and dysfunctions in cardio- vascular diseases. The potential therapeutic strategies by targeting Sirtuin 3 expression to improve mitochondrial function in cancer and cardiovascular diseases are summarized.