Sirtuin 4

SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.{{cite journal | vauthors = Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L | title = SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells | journal = Cell | volume = 126 | issue = 5 | pages = 941–54 |date=September 2006 | pmid = 16959573 | doi = 10.1016/j.cell.2006.06.057 | s2cid = 1391160 | doi-access = free }} A deacetylation of malonyl-CoA decarboxylase enzyme by SIRT4 represses the enzyme activity, inhibiting fatty acid oxidation in muscle and liver cells.{{cite journal | vauthors = Nasrin N, Wu X, Fortier E, Feng Y, Bare' OC, Chen S, Ren X, Wu Z, Streeper RS, Bordone L | title = SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. In primary myotubes and hepatocytes, knockdown of SIRT4 results in increased Fatty Acid Oxidation, cellular respiration, and pAMPK levels. SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes. | journal = J. Biol. Chem. | volume = 285 | issue = 42 | pages = 31995–32002 |date=October 2010 | pmid = 20685656 | pmc = 2952200 | doi = 10.1074/jbc.M110.124164 | doi-access = free }}{{cite journal | vauthors = Li S, Zheng W | title = Mammalian Sirtuins SIRT4 and SIRT7 | journal = Progress in Biophysics and Molecular Biology | series = Progress in Molecular Biology and Translational Science | volume = 154 | pages = 147–168 | date=2018 | doi = 10.1016/bs.pmbts.2017.11.001 | pmid = 29413176| isbn = 9780128122617 }} SIRT4 has a suppressive effect on peroxisome proliferator-activated receptor alpha (PPAR-α) which downregulates fatty acid oxidation in liver cells. Deacetylation of ADP/ATP translocase 2 (ANT2) increases cellular ATP by dampening mitochondrial uncoupling.

SIRT4 is a mitochondrial tumor suppressor protein. Overexpression of SIRT4 inhibits cancer cell proliferation by inhibition of glutamine metabolism.{{cite journal | vauthors = Yoo HC, Yu YC, Sung Y, Han JM| title = Glutamine reliance in cell metabolism | journal = Experimental & Molecular Medicine | volume = 52 | issue = 9 | pages = 1496–1516 | date=2020 | doi = 10.1038/s12276-020-00504-8 | pmid = 32943735| pmc = 8080614 | doi-access = free }}

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