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Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5
Open accessAbstract
We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.
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“This work resulted in the identification of novel modifications targeted by SIRT5: succinylation, malonylation and glutarylation as described in details below ((Du et al. 2011{Zhang, 2011 #16);(Peng et al. 2011);(Tan et al. 2014)}.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“SIRT5 positively regulates CPS1 activity by mediating desuccinylation, deglutarylation and possibly by deacetylation across multiple sites ((Du et al. 2011))((Tan et al. 2014))((Nakagawa et al. 2009)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“Mice lacking SIRT5 fail to upregulate CPS1 activity and show elevated blood ammonia under these conditions ((Nakagawa et al. 2009))((Tan et al. 2014)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“Moreover, HMGCS2 is also subject to glutarylation and malonylation ((Tan et al. 2014))((Nishida et al. 2015)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“Interestingly, lysine 88 is also a target of succinylation and glutarylation ((Rardin, He, et al. 2013))((Tan et al. 2014)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“Both MnSOD and the various mitochondrial superoxide sources are acylated ((Rardin, Newman, et al. 2013), (Rardin, He, et al. 2013);(Tan et al. 2014)); MnSOD also carries glutarylation, succinylation, and acetylation at functionally required lysine residues near its active site, K122 in particular bears all three modifications ((Tao et al. 2010)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Tan et al. 2014
In the citing paper
“Mass-spectrometry data has shown that there are an abundance of histone crotonylation sites in all four core histones22,40.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [40]
In the citing paper
“For example, SIRT5 exhibits efficient activity to lysine desuccinylation, demalonylation and glutarylation12-14”
From HDAC8 catalyzes the hydrolysis of long chain fatty acyl lysine (2016) · cites this paper as [14]
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Citations
Cites
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“Bioinformatic Analyses of Kglu Substrates To identify the possible association of Kglu substrates with cellular functions, we carried out gene ontology (GO) enrichment analysis using DAVID bioinformatics resources (Huang et al., 2009).”
MethodThe metabolic and molecular bases of inherited disease
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Self-citationAMPK: a nutrient and energy sensor that maintains energy homeostasis
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“In addition to histones, PTM-regulatory enzymes, such as AMP-activated protein kinase (AMPK) and lysine deacetylases (KDACs or HDACs), can control activity of their substrates (Chalkiadaki and Guarente, 2012; Hardie et al., 2012), many of which are metabolic enzymes.”
BackgroundTranscriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
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“For example, acetyl-CoA, SAM, NAD+, and a-ketoglutarate are donors/substrates or cofactors for histone lysine-modifying enzymes, i.e., those modulating levels of acetylation and methylation (Imai et al., 2000; Takahashi et al., 2006; Tsukada et al., 2006; Wellen et al., 2009).”
BackgroundInfluentialThe complex language of chromatin regulation during transcription
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“These PTM enzymes have important roles in modulation of chromatin structure and transcriptional regulation (Berger, 2007; Chi et al., 2010).”
BackgroundATP-citrate lyase links cellular metabolism to histone acetylation
Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1164097 · Cited by 2,298 · cited 2×
“For example, acetyl-CoA, SAM, NAD+, and a-ketoglutarate are donors/substrates or cofactors for histone lysine-modifying enzymes, i.e., those modulating levels of acetylation and methylation (Imai et al., 2000; Takahashi et al., 2006; Tsukada et al., 2006; Wellen et al., 2009).”
BackgroundHistone demethylation by a family of JmjC domain-containing proteins
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“For example, acetyl-CoA, SAM, NAD+, and a-ketoglutarate are donors/substrates or cofactors for histone lysine-modifying enzymes, i.e., those modulating levels of acetylation and methylation (Imai et al., 2000; Takahashi et al., 2006; Tsukada et al., 2006; Wellen et al., 2009).”
BackgroundSelf-citationTan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.008 · Cited by 1,902 · cited 3×
“Our previous studies identified new lysine acylation modifications on histones (Chen et al., 2007; Tan et al., 2011; Xie et al., 2012), including lysine crotonylation and succinylation, revealing potential crosstalk between cellular physiology and gene transcription.”
BackgroundSelf-citationProtein Structure Modeling with MODELLER
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Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
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“coli and HeLa cells, we used an affinity enrichment-based proteomics approach as previously described (Chen et al., 2012; Kim et al., 2006).”
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Items 301–400 of 877
A continuous sirtuin activity assay without any coupling to enzymatic or chemical reactions
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Potent and Selective Inhibitors of Human Sirtuin 5
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“Recent research has revealed novel catalytic functions for sirtuins, such as deacylation [3, 4], desuccinylation [5–8], deglutarylat ion [9], demalonylat ion [7, 10], and decrotonylation [11], with SIRT5 preferentially targeting succinyl, glutaryl, and malonyl moieties [5–10, 12].”
Self-citationChemical and Physiological Features of Mitochondrial Acylation
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“Mitochondrial lysine succinylation, malonylation, and glutarylation increase in SIRT5 KO tissue and cells, mirroring the acyl chain specificity of SIRT5 (Nishida et al., 2015; Park et al., 2013; Rardin et al., 2013b; Tan et al., 2014).”
BackgroundMitochondrial regulation of cardiac aging
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Histone malonylation is regulated by SIRT5 and KAT2A
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“In light of the observations and adverse effect of nucleolar expansion in both premature and physiological aging (Buchwalter and Hetzer, 2017; Tiku et al., 2016), we tested whether lysine malonylation could be involved in the aging process.”
BackgroundThe role of mammalian sirtuins in cancer metabolism
Sebastián, C., & Mostoslavsky, R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.07.008 · Cited by 39
The Causes and Consequences of Nonenzymatic Protein Acylation
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“modifications on proteins in vivo [1-7].”
BackgroundMethodOne-Atom Substitution Enables Direct and Continuous Monitoring of Histone Deacylase Activity
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Self-citationNew insights into the pathophysiology of methylmalonic acidemia
Head, P. E., Meier, J. L., & Venditti, C. P. (2023) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12617 · Cited by 40
“Similar to SIRT3, SIRT5 also upregulates ketogenesis and β-oxidation through desuccinylation of HMGCS2 and hydroxyacyl-CoA dehydrogenase (HADHA), respectively(96,102) while protecting against ammonia accumulation through deacylation and activation of CPS1 in the urea cycle.(73,94,98,103) SIRT5 can also upregulate amin…”
BackgroundSubstrate and Functional Diversity of Protein Lysine Post-translational Modifications
Hao, B., Chen, K., Zhai, L., Liu, M., Liu, B., & Tan, M. (2024) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzae019 · Cited by 41
“Acidic acylations include malonylation (Kmal) [77], Ksucc [77], and glutarylation (Kglu) [78].”
Self-citationThe role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome
Traba, J., & Sack, M. N. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2431-7 · Cited by 37
“Most sirtuins are lysine deacetylases, although SIRT5 has been shown to catalyze the desuccinylation, demalonylation and deglutarylation of lysines [21, 22].”
BackgroundKlimova, N., Long, A., & Kristián, T. (2017) · Translational Stroke Research · doi:10.1007/s12975-017-0569-8 · Cited by 36
“Furthermore, it was shown that SIRT5 can act as a desuccinylase [82, 83] and also as a lysine deglutarylase [84].”
Prediction of lysine glutarylation sites by maximum relevance minimum redundancy feature selection
Ju, Z., & He, J. (2018) · Analytical Biochemistry · doi:10.1016/j.ab.2018.04.005 · Cited by 40
RF-GlutarySite: a random forest based predictor for glutarylation sites
AL-barakati, H. J., Saigo, H., Newman, R. H., & KC, D. B. (2019) · Molecular Omics · doi:10.1039/c9mo00028c · Cited by 39
The Growing Landscape of Succinylation Links Metabolism and Heart Disease
Yang, L., Miao, S., Zhang, J., Wang, P., Liu, G., & Wang, J. (2021) · Epigenomics · doi:10.2217/epi-2020-0273 · Cited by 39
SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein
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“It is only a weak protein deacetylase, but it efficiently removes longer-chain acyl groups from proteins, such as succinyl, malonyl or glutaryl groups (23, 24).”
InfluentialAcylations in cardiovascular biology and diseases, what's beyond acetylation
Sun, X., Zhang, Y., Chen, X., & Tang, X. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104418 · Cited by 38
Self-citationShen, H., Ma, W., Hu, Y., Liu, Y., Song, Y., Fu, L., & Qin, Z. (2024) · Theranostics · doi:10.7150/thno.97320 · Cited by 38
“SIRT5's ability to remove succinyl, malonyl, and glutaryl groups from lysine residues on proteins influences several key metabolic processes [42, 43].”
BackgroundLactate and lysine lactylation of histone regulate transcription in cancer
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“Besides transcriptional regulation (C/EBP, glucocorticoid receptor, CREB and HNF3) and the allosteric cofactor NAG [7, 17], recent mechanistic studies have also underscored the importance of posttranslational modifications (PTMs) for CPS1 protein activity [11–13, 47].”
BackgroundJames, A. M., Smith, A. C., Smith, C. L., Robinson, A. J., & Murphy, M. P. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.007 · Cited by 36
Lysine glutarylation in human sperm is associated with progressive motility
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Metabolomics Based Identification of SIRT5 and Protein Kinase C Epsilon Regulated Pathways in Brain
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“…distinct from SIRT3, the major mitochondrial deacetylase, and SIRT4, which mediates ADP-ribosylation and has lipoamidase activity, in that it acts specifically on succinyl- (Rardin et al., 2013), malonyl(Nishida et al., 2015), and glutaryl- (Tan et al., 2014) lysine posttranslational modifications.”
BackgroundMethodInfluentialIshiguro, T., Tanabe, K., Kobayashi, Y., Mizumoto, S., Kanai, M., & Kawashima, S. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-26114-z · Cited by 38
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“Of note, SIRT5 also catalyzes lysine demalonylation and deglutarylation (13, 14).”
BackgroundCPS1: Looking at an ancient enzyme in a modern light
Nitzahn, M., & Lipshutz, G. S. (2020) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2020.10.003 · Cited by 36
iGlu_AdaBoost: Identification of Lysine Glutarylation Using the AdaBoost Classifier
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Biochemical genesis of enzymatic and non-enzymatic post-translational modifications
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Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses
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Self-citationStructure‐based discovery of new selective small‐molecule sirtuin 5 inhibitors
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Post-translational Acetylation Control of Cardiac Energy Metabolism
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“A few studies suggest that some of the nuclear acetyltransferases, such as p300/CBP, may shuttle between the nucleus and cytoplasm and participate in the acetylation of cytosolic proteins (44, 50, 51).”
BackgroundIntegrative Chemical Biology Approaches to Deciphering the Histone Code: A Problem-Driven Journey
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Epigenetic Regulation of Ferroptosis in Central Nervous System Diseases
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Amino acids downregulate SIRT4 to detoxify ammonia through the urea cycle
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Succinylation modification: a potential therapeutic target in stroke
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“Finally, only English articles were included in our search, which may exclude relevant studies in other languages.”
BackgroundRecent Advances in Inhibitors of Sirtuin1/2: An Update and Perspective
Zhou, Z., Ma, T., Zhu, Q., Xu, Y., & Zha, X. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0207 · Cited by 34
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Activation and inhibition of sirtuins: From bench to bedside
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Posttranslational lysine 2-hydroxyisobutyrylation of human sperm tail proteins affects motility
Cheng, Y.-M., Peng, Z., Chen, H., Pan, T.-T., Hu, X.-N., Wang, F., & Luo, T. (2019) · Human Reproduction · doi:10.1093/humrep/dez296 · Cited by 32
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“, 2013) and mediates protein desuccinylation, demalonylation, and deglutarylation (Du et al., 2011; Tan et al., 2014; Hirschey and Zhao, 2015; Kumar and Lombard, 2018).”
BackgroundSirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
Haschler, T. N., Horsley, H., Bałys, M., Anderson, G. W., Taanman, J., Unwin, R. J., & Norman, J. T. (2021) · Scientific Reports · doi:10.1038/s41598-021-94185-6 · Cited by 33
Probing lysine posttranslational modifications by unnatural amino acids
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An improved fluorogenic assay for SIRT1, SIRT2, and SIRT3
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Mitochondrial Enzymes of the Urea Cycle Cluster at the Inner Mitochondrial Membrane
Haskins, N., Bhuvanendran, S., Anselmi, C., Gams, A., Kanholm, T., Kocher, K. M., LoTempio, J. E., Krohmaly, K. I., Sohai, D. K., Stearrett, N., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.542950 · Cited by 31
“Moreover, patients with urea cycle defects who receive a liver transplant continue to need supplementation with arginine (Tuchman 1989).”
BackgroundGlobal Profiling of 2-Hydroxyisobutyrylome in Common Wheat
Zhang, N., Zhang, L., Li, L., Geng, J., Zhao, L., Ren, Y. N., Dong, Z., & Chen, F. (2021) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2020.06.008 · Cited by 31
Melo, M. G., Remacle, N., Cudré-Cung, H.-P., Roux, C., Poms, M., Cudalbu, C., Barroso, M., Gersting, S. W., Feichtinger, R. G., Mayr, J. A., et al. (2021) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2021.03.017 · Cited by 30
The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer
Onyiba, C. I., Scarlett, C. J., & Weidenhofer, J. (2022) · Cancers · doi:10.3390/cancers14205118 · Cited by 31
A SARS-CoV-2 –human metalloproteome interaction map
Chasapis, C. T., Georgiopoulou, A. K., Perlepes, S. P., Bjørklund, G., & Peana, M. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111423 · Cited by 30
A glimpse into novel acylations and their emerging role in regulating cancer metastasis
Shi, H., Cui, W., Qin, Y., Chen, L., Yu, T., & Lv, J. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-05104-z · Cited by 35
“Lysine glutarylation (Kglu) was first detected and comprehensively validated in 2014 through immunoblot and MS, combined with chemical and biochemical methods [72].”
BackgroundMethodInfluentialDu, Y., Zhai, Z., Li, Y., Lü, M., Cai, T., Zhou, B., Huang, L., Wei, T., & Li, T. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00240 · Cited by 30
Cui, Y., Li, X., Lin, J., Hao, Q., & Li, X. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00713 · Cited by 30
Simithy, J., Sidoli, S., & Garcia, B. A. (2018) · PROTEOMICS · doi:10.1002/pmic.201700309 · Cited by 31
Huang, K., Kao, H.-J., Hsu, J. B., Weng, S., & Lee, T.-Y. (2019) · BMC Bioinformatics · doi:10.1186/s12859-018-2394-9 · Cited by 30
Recent Progress on the Discovery of Sirt2 Inhibitors for the Treatment of Various Cancers
Wang, T., Xu, Z., Lu, Y., Shi, J., Liu, W., Zhang, C., Jiang, Z., Qi, B., & Bai, L. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190510103416 · Cited by 30
Mitochondrial sirtuins in stem cells and cancer
Jaiswal, A., Xudong, Z., Ju, Z., & Saretzki, G. C. (2021) · FEBS Journal · doi:10.1111/febs.15879 · Cited by 29
Wang, X. R., Ding, Z., Wang, R., & Lin, X. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbac631 · Cited by 33
Zhu, D. Z., Liu, J., Duan, W., Sun, H., Zhang, L., & Yan, Y. (2023) · Journal of Experimental Botany · doi:10.1093/jxb/erad006 · Cited by 29
Mitochondrial functions in stem cells
Margineantu, D. H., & Hockenbery, D. M. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.004 · Cited by 29
Mitochondrial Sirtuins in Skin and Skin Cancers
Su, S., Ndiaye, M. A., Singh, C. K., & Ahmad, N. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13254 · Cited by 29
Xue, C., Qiao, Z., Chen, X., Cao, P., Liu, K., Liu, S., Lu, Y., & Gong, Z. (2020) · Rice · doi:10.1186/s12284-020-00389-1 · Cited by 30
Profiling of post-translational modifications by chemical and computational proteomics
Yang, F., & Wang, C. (2020) · Chemical Communications · doi:10.1039/d0cc05447j · Cited by 31
Demalonylation of DDX3 by Sirtuin 5 promotes antiviral innate immune responses
He, X., Li, T., Qin, K., Luo, S., Li, Z., Ji, Q., Song, H., He, H., Tang, H., Han, C., et al. (2021) · Theranostics · doi:10.7150/thno.52934 · Cited by 29
“Sirt5, which resides mostly in the mitochondria and partly in the cytoplasm, is a deacetylase that removes lysine succinylation, malonylation, and glutarylation from targeted proteins [20, 25, 38].”
BackgroundNAD+ Homeostasis in Diabetic Kidney Disease
Xu, J., Kitada, M., & Koya, D. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.703076 · Cited by 30
Yang, Y., Zhang, H., Guo, Z., Zou, S., Long, F., Wu, J., Li, P., Zhao, G., & Zhao, W. (2021) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2021.100148 · Cited by 29
“Published by Elsevier Inc on behalf of American Society for Bio This is an open access article under the CC BY-NC-ND license (http://creativecommons development of high-resolution MS and immunoaffinity purification technology, diverse acylations on lysine, including acetylation (3, 4), succinylation (5), malonylation…”
BackgroundChemical Biology Tools for Protein Lysine Acylation
Xie, Y., Du, S., Liu, Z., Liu, M., Xu, Z., Wang, X., Kee, J. X., Yi, F., Sun, H., & Yao, S. Q. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202200303 · Cited by 29
Mitochondrial sirtuins: Energy dynamics and cancer metabolism
Lee, H., & Yoon, H. (2024) · Molecules and Cells · doi:10.1016/j.mocell.2024.100029 · Cited by 28
Ouyang, S., Zhu, J., Cao, Q., Liu, J., Zhang, Z., Zhang, Y., Wu, J., Sun, S., Fu, J., Chen, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202305715 · Cited by 27
Self-citationRegulation of urea cycle by reversible high-stoichiometry lysine succinylation
Zhang, R., Fang, J., Xie, X., Carrico, C., Meyer, J. G., Wei, L., Bons, J., Rose, J., Riley, R. R., Kwok, R., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01005-y · Cited by 29
“Instead, SIRT5 mainly functions as a demalony-lase 1,13 , desuccinylase 1 and deglutarylase 31 .”
Self-citationNemeria, N. S., Gerfen, G. J., Yang, L., Zhang, X., & Jordan, F. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.001 · Cited by 28
Yuan, H., Chen, J., Yang, Y., Shen, C., Xu, D., Wang, J., Yan, D., He, Y., & Zheng, B. (2019) · BMC Plant Biology · doi:10.1186/s12870-019-2072-8 · Cited by 28
Sirtuin 7 serves as a promising therapeutic target for cardiorenal diseases
Li, X., Zhang, Y.-P., Zhang, M.-W., Zhang, Z.-Z., & Zhong, J. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174977 · Cited by 28
Self-citationDu, Y., Hu, H., Hua, C., Du, K., & Wei, T. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.06.073 · Cited by 29
Sirtuin 5 Deficiency Does Not Compromise Innate Immune Responses to Bacterial Infections
Heinonen, T., Ciarlo, E., Théroude, C., Πελεκάνου, Α., Herderschee, J., Roy, D. L., & Roger, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02675 · Cited by 28
“SIRT5 is a weak deacetylase and recent data suggest that SIRT5 primarily performs lysine demalonylation, desuccinylation, and deglutarylation (10, 11).”
BackgroundMailloux, R. J. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103155 · Cited by 30
“Lysine glutarylation is also required to control mitochondrial metabolism [191].”
BackgroundSIRT5 regulates pancreatic β‑cell proliferation and insulin secretion in type 2 diabetes
Ma, Y., & Fei, X. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6301 · Cited by 28
Evolved, Selective Erasers of Distinct Lysine Acylations
Spinck, M., Neumann‐Staubitz, P., Ecke, M., Gasper, R., & Neumann, H. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202002899 · Cited by 27
Kokkinidis, M., Glykos, N. M., & Fadouloglou, V. E. (2020) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2020.05.001 · Cited by 27
Lagerwaard, B., Pougovkina, O., Bekebrede, A. F., Brinke, H. T., Wanders, R. J. A., Nieuwenhuizen, A. G., Keijer, J., & de Boer, V. C. J. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12296 · Cited by 26
Wasserfurth, P., Nebl, J., Rühling, M. R., Shammas, H., Bednarczyk, J., Koehler, K., Boßlau, T. K., Krüger, K., Hahn, A., & Das, A. M. (2021) · Nutrients · doi:10.3390/nu13113824 · Cited by 27
Sirtuin Oxidative Post-translational Modifications
Kalous, K., Wynia‐Smith, S. L., & Smith, B. C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.763417 · Cited by 28
Cyclic peptide-based potent human SIRT6 inhibitors
Liu, J., & Zheng, W. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c5ob02339d · Cited by 27
Olp, M. D., Zhu, N., & Smith, B. C. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00595 · Cited by 30
Post-translational modulation of cell signalling through protein succinylation
Kubatzky, K. F., Gao, Y., & Yu, D. (2023) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2023.00196 · Cited by 27
Vai, A., Noberini, R., Ghirardi, C., de Paula, D. R., Carminati, M., Pallavi, R., Araújo, N. V. P., Varga‐Weisz, P., & Bonaldi, T. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100799 · Cited by 26
“The enzyme p300 is the HAT with the broadest acylase capability, able to catalyze the deposition of propionyl, butyryl, crotonyl, β -hydroxybutyryl, succinyl, and glutaryl groups to lysine residues (6 – 9).”
Metadata
- Authors
- Tan, M., Peng, C., Anderson, K. A., Chhoy, P., Xie, Z., Dai, L., Park, J., Chen, Y., Huang, H., Zhang, Y., Ro, J., Wagner, G. R., Green, M. F., Madsen, A. S., Schmiesing, J., Peterson, B. S., Xu, G., Ilkayeva, O. R., Muehlbauer, M. J., Braulke, T., Mühlhausen, C., Backos, D. S., Olsen, C. A., McGuire, P. J., Pletcher, S. D., Lombard, D. B., Hirschey, M. D., & Zhao, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- University of Chicago (US)
- Duke University (US)
- University of Michigan (US)
- Technical University of Denmark (DK)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Colorado Anschutz (US)
- National Institutes of Health (US)
- Corresponding author
- Hirschey, Matthew D.
- Zhao, Yingming
- ORCID
- Tan, Minjia
- Peng, Chao
- Chhoy, Peter
- Xie, Zhongyu
- Dai, Lunzhi
- Huang, He
- Zhang, Yi
- Ro, Jennifer
- Green, Michelle F.
- Madsen, Andreas S.
- Xu, Guofeng
- Ilkayeva, Olga R.
- Muehlbauer, Michael J.
- Braulke, Thomas
- Mühlhausen, Chris
- Backos, Donald S.
- Olsen, Christian A.
- McGuire, Peter J.
- Pletcher, Scott D.
- Lombard, David B.
- Hirschey, Matthew D.
- Zhao, Yingming
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 19
- Issue
- 4
- Pages
- 605-617
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4108075
- OpenAlex
- W2088511656
- Cited by
- 844
- References
- 45
- Citations by year
- 2026: 49 · 2025: 63 · 2024: 86 · 2023: 50 · 2022: 79 · 2021: 106 · 2020: 67 · 2019: 74 · 2018: 80 · 2017: 53 · 2016: 70 · 2015: 50 · 2014: 16
- FWCI
- 32.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Funders
- Lundbeckfonden (R52-2010-5054)
- National Institutes of Health (UL1TR000430)
- National Institute on Alcohol Abuse and Alcoholism (AA022146, R01AA022146)
- National Institute on Aging (F31AG047696, R01AG045351, AG045351, P30AG013283, T32AG000114)
- National Cancer Institute (R21CA177925, CA160036, CA059365-19, U24CA160036, T32CA059365, CA177925)
- National Institute of General Medical Sciences (GM105933, T32GM007105, GM101171, T32GM007315, R01GM101171, R01GM105933)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK096493, P30DK020572)
- National Center for Research Resources (RR020839, U54RR020839)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- SIRT5, protein posttranslational modification, urea cycle, glutaric aciduria type I, glutaryl-CoA, mitochondrial proteins, metabolic enzymes
- MeSH terms
- Acyl Coenzyme A, Animals, Carbamoyl-Phosphate Synthase (Ammonia), Lysine, Models, Biological, Protein Processing, Post-Translational, Mass Spectrometry, Immunoblotting, Molecular Structure, Sirtuins, Proteomics, Mice
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