Sirtuin 4

Sirtuin 4 (SIRT4) is a protein that in humans is encoded by the SIRT4 gene. It is a member of the sirtuin family of proteins, which are homologs to the yeast Sir2 protein. Sirtuins are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of ribosomal DNA.

Function

SIRT4 is a mitochondrial enzyme that has ADP-ribosyltransferase activity and deacetylase activity, which is not NAD+-dependent. It plays a role in regulating the insulin secretion process, probably by modifying proteins such as GLUT2 with ADP-ribose, which affects their function, and/or by deacetylating key proteins in this pathway. It negatively regulates the effects of caloric restriction on mitochondrial biogenesis and the oxidative function of mitochondria.

Clinical significance

Alterations in SIRT4 expression have been associated with various diseases, including cancer, diabetes, and neurodegenerative diseases. In cancer, SIRT4 acts as a tumor suppressor by inhibiting glutamine metabolism. In diabetes, SIRT4 regulates insulin secretion by repressing the urea cycle. In neurodegenerative diseases, SIRT4 has been implicated in the regulation of mitochondrial function and neuronal survival.

See also

• Sirtuin
• Mitochondria
• Insulin
• Cancer
• Diabetes
• Neurodegenerative diseases