Sirtuin 4
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Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene.[1][2] 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
[edit | edit source]SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.[3] A deacetylation of malonyl-CoA decarboxylase enzyme by SIRT4 represses the enzyme activity, inhibiting fatty acid oxidation in muscle and liver cells.[4][5] SIRT4 has a suppressive effect on peroxisome proliferator-activated receptor alpha (PPAR-α) which downregulates fatty acid oxidation in liver cells.[5] Deacetylation of ADP/ATP translocase 2 (ANT2) increases cellular ATP by dampening mitochondrial uncoupling.[5]
Clinical significance
[edit | edit source]SIRT4 is a mitochondrial tumor suppressor protein.[5] Overexpression of SIRT4 inhibits cancer cell proliferation by inhibition of glutamine metabolism.[5][6]
Ligands
[edit | edit source]- Inhibitors
References
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Further reading
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
