SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells.

By M. Haigis, R. Mostoslavsky, K. Haigis, Kamau Fahie, Danos C. Christodoulou, A. Murphy, D. Valenzuela, G. Yancopoulos, M. Karow, G. Blander and 5 more. Cell, 2006

1,197 citations recorded by the source corpus.

Subfields: Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/67dd24d22102e6bc2accc75572bed82fafab7fa3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Geriatrics and Gerontology

1. Johan Auwerx
2. D. Sinclair
3. E. Verdin
4. L. Guarente
5. M. Haigis
6. C. Cantó
7. R. Houtkooper
8. Joseph A. Baur

In Physiology

1. Johan Auwerx
2. D. Sinclair
3. E. Verdin
4. C. Cantó
5. R. Houtkooper
6. M. Haigis
7. L. Guarente
8. Joseph A. Baur

Citations in the corpus

• NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “Furthermore, SIRT4 uses NAD to ADP-ribosylate and reduce GDH activity, thereby inhibits insulin secretion in response to amino acids in β cells.(227) SIRT5 is an NAD-dependent lysine desuccinylase, demalonylase, and deglutarylase.”
• A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice (2008, background): “Given that overexpression of SIRT1 in mice does induce physiological alterations consistent with CR [32], it is possible that CR impacts the levels of SIRT1 and other sirtuins in other tissues that play a central role in regulating metabolism, such the pancreas [33,34].”
• Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, neutral): “There are variants on this theme: SIRT5 and SIRT6 have desuccinylation and defatty-acylation activities, respectively (Du et al., 2011; Jiang et al., 2013), while SIRT4 and SIRT6 can simply liberate NAM, leaving a covalently attached mono-ADP-ribose (Haigis et al., 2006; Liszt et al., 2005).”
• SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle (2009, positive): “SIRT4 transfers ADP-ribose from NAD to glutamate dehydrogenase (GDH), an enzyme that converts glutamate to a-ketoglutarate, thereby repressing this enzymatic activity (Ahuja et al., 2007; Haigis et al., 2006).”
• NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “However, deacetylation is not the singular function of all sirtuins, as SIRT4 can act as a lipoamidase (Mathias et al., 2014) and, along with SIRT6, as an NAD+-dependent mono-ADP-ribosyltransferase (Haigis et al., 2006; Liszt et al., 2005).”
• Sirtuin Regulation of Mitochondria - Energy Production, Apoptosis, and Signaling (2010, background): “So far, only ADPribosyltransferase activity has been described for SIRT4 [20,21].”
• A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis (2008, background): “Given previous observations demonstrating that Sirt3 deacetylates GDH and AceCS2 (11–13) and our observations here regarding Complex I, the effects of Sirt3 on ATP levels are undoubtedly complex and presumably represent the coordinated regulation of both substrate flow to the mitochondria and the ET”
• Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. (2013, background): “GLUD1 was previously shown to be regulated by SIRT4-dependent ADP-ribosylation in pancreatic b cells (Haigis et al., 2006).”
• Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation (2007, background): “We cannot exclude the possibility that SIRT4 and SIRT5 deacetylate specific mitochondrial factors not detected by our methodology.”
• REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS (2010, positive): “Deacetylation by Sirt3 under caloric restriction activated glutamate dehydrogenase (GDH) [92] while ADP-ribosylation by Sirt4 repressed GDH activity and decreased ATP production due to reduced trafficking through tricarboxylic acid cycle intermediates [88].”
• Sirtuins: critical regulators at the crossroads between cancer and aging (2007, background): “SIRT4 ADP-ribosylates and represses glutamate dehydrogenase (GDH) to suppress insulin signaling.”