SIRT3 interactions with FOXO3 acetylation, phosphorylation and ubiquitinylation mediate endothelial cell responses to hypoxia.

The endothelial cells (ECs) that line the vascular lumen are exposed to a wide variety of environmental stresses, such as hypoxia. Maladaptation to stress in ECs is a key event in the development of cardiovascular disease. Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase that modulates various proteins to control mitochondrial function and metabolism.

SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage.

Progressive accumulation of defective mitochondria is a common feature of aged cells. SIRT3 is a NAD(+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. FOXO3 is a direct target of SIRT3 and functions as a forkhead transcription factor to govern diverse cellular responses to stress.