Sirtuin 4
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene.[5][6] SIRT4 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT4 exhibits NAD+-dependent deacetylase activity.
Function
SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.[7] A deacetylation of malonyl-CoA decarboxylase enzyme by SIRT4 represses the enzyme activity, inhibiting fatty acid oxidation in muscle and liver cells.[8][9] SIRT4 has a suppressive effect on peroxisome proliferator-activated receptor alpha (PPAR-α) which downregulates fatty acid oxidation in liver cells.[9] Deacetylation of ADP/ATP translocase 2 (ANT2) increases cellular ATP by dampening mitochondrial uncoupling.[9]
Clinical significance
SIRT4 is a mitochondrial tumor suppressor protein.[9] Overexpression of SIRT4 inhibits cancer cell proliferation by inhibition of glutamine metabolism.[9][10]
Ligands
- Inhibitors
