, unlike other sirtuins, mostly functions as a histone ADP-ribosyltransferase but does not have NAD-dependent deacetylase activity .
Haigis et al., "SIRT4
inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic [beta] cells," Cell, vol.
Shen, "MicroRNA-497 inhibits cardiac hypertrophy by targeting Sirt4
," PLoS ONE, vol.
As discussed above, other Sirtuins, especially, SIRT4
is also a mitochondrial deacetylase as SIRT3 and functions as tumor suppressor via modulating glutamine metabolism.
SIRT3 and SIRT4
are mitochondrial tumor suppressor proteins that connect mitochondrial metabolism and carcinogenesis.
, a less studied mitochondrial sirtuin, is an integral part of the metabolic response to genotoxic stress.
, a member of sirtuin family exclusively localized in mitochondria, plays an important role in mitochondrial metabolism .
The Sirt family includes several members localized in different subcellular compartments: the nuclei (Sirtl, Sirt2, Sirt6, and Sirt7), cytoplasms (Sirtl and Sirt2), and mitochondria (Sirt3, Sirt4
, and Sirt5) [9, 10].
In addition SIRT4
, SIRT6, and SIRT7 exhibit monoadenosine diphosphate(ADP-) ribosyltransferase activity.
An et al., "SIRT4
accelerates Ang II-induced pathological cardiac hypertrophy by inhibiting manganese superoxide dismutase activity," European Heart Journal, vol.
It is acknowledged that the silent information regulator 2 (SIR2) complex is composed of 4 groups, including group I with sirtuin 1 (Sirtl), 2, and 3; group II with Sirt4
; group III with Sirt5; and group IV with Sirt6 and 7 .
Despite conserved deacetylase domains, mitochondrial sirtuin 4 (Sirt4
) is the most efficient lipoamidase among mitochondrial sirtuins.