Regulation of SIRT1 protein levels by nutrient availability

Kanfi, Yariv; Peshti, Victoria; Gozlan, Yosi M.; Rathaus, M.; Gil, Reuven; Cohen, Haim Y.

doi:10.1016/j.febslet.2008.06.005

Cited by 117 publications

(83 citation statements)

References 32 publications

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“…More strikingly, Sajish and Schimmel recently found that serum starvation or resveratrol addition promotes the nuclear translocation of TyrRS, which enhances the interaction of TyrRS with PARP1 and increases the PARP1 activity (6). However, serum starvation increases SIRT1 protein expression, thereby inhibiting the function of PARP1 (16,40). Thus, the function of this regulatory network remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

Cao

Xiao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/ CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD + -dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner. Oxidative stress increases the level of PCAF and decreases the level of SIRT1 and deacetylase activity, all of which promote the nuclear translocation of hyperacetylated TyrRS. Furthermore, TyrRS is primarily acetylated on the K244 residue near the nuclear localization signal (NLS), and acetylation inhibits the aminoacylation activity of TyrRS. Molecular dynamics simulations have shown that the in silico acetylation of K244 induces conformational changes in TyrRS near the NLS, which may promote the nuclear translocation of acetylated TyrRS. Herein, we show that the acetylated K244 residue of TyrRS protects against DNA damage in mammalian cells and zebrafish by activating DNA repair genes downstream of transcription factor E2F1. Our study reveals a previously unknown mechanism by which acetylation regulates an aminoacyl-tRNA synthetase, thus affecting the repair pathways for damaged DNA.

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Section: Discussionmentioning

confidence: 99%

Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

Cao

Xiao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…9, A and B). Likewise, nutrient depletion activates Sirt1, an upstream activator of FoxO transcription factors both in vitro and in vivo (47,48). Sirt1 protein was significantly increased (1.5-fold) in the starved mouse heart compared with fed mouse heart (Fig.…”

Section: Starvation Activates Foxo Transcription Factors and Induces mentioning

confidence: 97%

FoxO Transcription Factors Promote Autophagy in Cardiomyocytes

Sengupta

Molkentin

Yutzey

2009

Journal of Biological Chemistry

388

304

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“…We observed that 48-h-fasting induced decreased T 3 and T 4 levels and increased hepatic SIRT1 content. Other reports in the literature have already described, independently, fasting-induced decreased TH levels (Diano et al 1998, Hashimoto et al 2001) and hepatic SIRT1 content increment (Rodgers et al 2005, Kanfi et al 2008. Reduced TH concentration serves to conserve energy, as these hormones are important stimulators of basal metabolism and thermogenesis (Klieverik et al 2009).…”

Section: Sirt1 Regulation By Th Involves Trbmentioning

confidence: 99%

“…It is very well established that physiological adaptation to fasting involves the suppression of TH production, as a mechanism to conserve energy (Boelen et al 2008). In addition, recent studies have shown the fasting-induced rise in SIRT1 expression in several tissues (Rodgers et al 2005, Kanfi et al 2008. Therefore, the existence of common metabolic routes regulated by TH and SIRT1, together with the inverse correlation of these factors' variation during calorie deprivation, led us to investigate whether SIRT1 expression is regulated by TH in mice and the possible interactions of TH and SIRT1 during energy deprivation.…”

Section: Introductionmentioning

confidence: 99%

“…SIRT1 has been associated with decreased white fat depot accumulation (Picard et al 2004), increased hepatic and muscular lipid catabolism (Feige et al 2008, Purushotham et al 2009, increased gluconeogenesis (Rodgers & Puigserver 2007), and improvement of insulin sensitivity (Sun et al 2007, Feige et al 2008, Pfluger et al 2008. These punctual contributions are extremely valuable to understand the essential role of SIRT1 in adaptation to calorie restriction and fasting, conditions that are able to trigger SIRT1 protein expression in various tissues (Cohen et al 2004, Kanfi et al 2008, by still unknown mechanisms. On the contrary, consumption of an excessive high-fat diet is generally accompanied by reduced SIRT1 levels (Deng et al 2007), and, if SIRT1 expression or activity is restored, adverse effects induced by high-fat diet ingestion are attenuated (Baur et al 2006, Feige et al 2008, Pfluger et al 2008.…”

Section: Introductionmentioning

confidence: 99%

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Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice

Cordeiro¹,

Souza²,

Oliveira³

et al. 2012

Journal of Endocrinology

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Sirtuin 1 (SIRT1), a NAD C -dependent deacetylase, has been connected to beneficial effects elicited by calorie restriction. Physiological adaptation to starvation requires higher activity of SIRT1 and also the suppression of thyroid hormone (TH) action to achieve energy conservation. Here, we tested the hypothesis that those two events are correlated and that TH may be a regulator of SIRT1 expression. Forty-eight-hour fasting mice exhibited reduced serum TH and increased SIRT1 protein content in liver and brown adipose tissue (BAT), and physiological thyroxine replacement prevented or attenuated the increment of SIRT1 in liver and BAT of fasted mice. Hypothyroid mice exhibited increased liver SIRT1 protein, while hyperthyroid ones showed decreased SIRT1 in liver and BAT. In the liver, decreased protein is accompanied by reduced SIRT1 activity and no alteration in its mRNA. Hyperthyroid and hypothyroid mice exhibited increases and decreases in food intake and body weight gain respectively. Food-restricted hyperthyroid animals (pair-fed to euthyroid group) exhibited liver and BAT SIRT1 protein levels intermediary between euthyroid and hyperthyroid mice fed ad libitum. Mice with TH resistance at the liver presented increased hepatic SIRT1 protein and activity, with no alteration in Sirt1 mRNA. These results suggest that TH decreases SIRT1 protein, directly and indirectly, via food ingestion control and, in the liver, this reduction involves TRb. The SIRT1 reduction induced by TH has important implication to integrated metabolic responses to fasting, as the increase in SIRT1 protein requires the fasting-associated suppression of TH serum levels.

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Regulation of SIRT1 protein levels by nutrient availability

Cited by 117 publications

References 32 publications

Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

FoxO Transcription Factors Promote Autophagy in Cardiomyocytes

Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice

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