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structural model of a complex of human Sirt4 and GDH (zeige GLUD1 Proteine) in order to elucidate the molecular mechanism underlying the ADP-ribosylation of GDH (zeige GLUD1 Proteine) by Sirt4
we propose that the SIRT4-OPA1 (zeige OPA1 Proteine) axis is causally linked to mitochondrial dysfunction and altered mitochondrial dynamics that translates into aging-associated decreased mitophagy based on an unbalanced mitochondrial fusion/fission cycle.
SIRT4 protein levels in endometrioid adenocarcinoma were markedly lower than its non-neoplastic tissue counterpart (P< 0.001).
The function of the three mitochondrial sirtuins (SIRT3 (zeige SIRT3 Proteine), SIRT4, SIRT5 (zeige SIRT5 Proteine)) and their role in disease are reviewed.
Protein levels of SIRT 4 were significantly higher in HUVECs from HELLP pregnancies compared to control after 60 and 120 minutes of hypoxia.
we found that knock-out of mitochondrial sirtuin (zeige SIRT1 Proteine) sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated
This is the first study to identify an association between SIRT4 expression and decreased mitochondrial fission, which was driven by Drp1. SIRT4 inhibited Drp1 phosphorylation and weakened Drp1 recruitment to the mitochondrial membrane via an interaction with Fis-1.
miR (zeige MLXIP Proteine)-15b is a negative regulator of stress-induced SIRT4 expression, thereby counteracting senescence associated mitochondrial dysfunction and regulating the SASP (zeige ASPRV1 Proteine) and possibly organ aging, such as photoaging of human skin.
SIRT4 overexpression inhibits the proliferation of colorectal cancer cells in vitro and in vivo.
Data indicate that compared to non-neoplastic endometria (NNE), endometrial cancer (EC) showed SIRT7 (zeige SIRT7 Proteine) mRNA overexpression, whereas SIRT1 (zeige SIRT1 Proteine), SIRT2 (zeige SIRT2 Proteine), SIRT4 and SIRT5 (zeige SIRT5 Proteine) were underexpressed, and no significant differences were observed for SIRT3 (zeige SIRT3 Proteine) and SIRT6 (zeige SIRT6 Proteine).
SIRT4 is downregulated in cardiomyocytes after myocardial ischemia-reperfusion (MI-R), ameliorates MI-R injury, preserves mitochondrial function and reduces cardiomyocyte apoptosis after MI-R.
Data suggest that high-fat diet (HFD) alters regulation of expression of sirtuins (Sirt4 and Sirt7 (zeige SIRT7 Proteine)) and enzymes in NAD biosynthetic pathway (Tdo2 (zeige TDO2 Proteine) and Nnmt (zeige NNMT Proteine)); these alterations are more prominent in liver as compared to white adipose tissue or skeletal muscle; Tdo2 (zeige TDO2 Proteine) and Nnmt (zeige NNMT Proteine) may serve as markers of HFD consumption. (Tdo2 (zeige TDO2 Proteine) = tryptophan 2,3-dioxygenase (zeige TDO2 Proteine); Nnmt (zeige NNMT Proteine) = nicotinamide N-methyltransferase (zeige NNMT Proteine))
These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin (zeige INS Proteine) secretion and glucose homeostasis during aging.
miR (zeige MLXIP Proteine)-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course.
Until now, a mammalian cellular lipoamidase has not been characterized; this study discovered that SIRT4 can function with this enzymatic capacity in the mitochondria, and that PDH (zeige PDP Proteine) is a biological substrate; compared to its catalytic efficiency for deacetylation, SIRT4 exhibits far superior enzymatic activity for lipoyl- and biotinyl-lysine modifications.
The results of this study indicated a critical and novel stress response role for SIRT4 in promoting proper glutamate (zeige GRIN1 Proteine) transport capacity and protecting against excitotoxicity
regulates ATP levels via ANT2 (zeige SLC25A5 Proteine) and a feedback loop involving AMPK (zeige PRKAA1 Proteine)
these results highlight the tumor-suppressive role of SIRT4 in Myc-induced B cell lymphoma and suggest that SIRT4 may be a potential target against Myc-induced and/or glutamine-dependent cancers.
The enhanced fatty acid oxidation observed in SIRT4 knockout hepatocytes requires functional SIRT1 (zeige SIRT1 Proteine), demonstrating a clear cross talk between mitochondrial and nuclear sirtuins.
Data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest, and tumor suppression.
This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family 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 rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family.
sirtuin (silent mating type information regulation 2 homolog) 4 (S. cerevisiae)
, sirtuin 4
, NAD-dependent ADP-ribosyltransferase sirtuin-4
, NAD-dependent protein deacetylase sirtuin-4
, SIR2-like protein 4
, regulatory protein SIR2 homolog 4
, sir2-like 4
, sirtuin type 4
, NAD-dependent deacetylase sirtuin-4