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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
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Lipoic acid metabolism and mitochondrial redox regulation
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“More recently, SIRT5 was reported to regulate lysine glutarylation levels, thereby modulating the activity of carbamoyl phosphase synthase 1, a critical enzyme in the urea cycle (Tan et al., 2014).”
BackgroundMetabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation
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“SIRT5 possesses unique enzymatic activity on hydrolyzing negatively charged lysine modifications such as lysine succinylation, malonylation, and glutarylation (1, 4, 8).”
BackgroundInfluentialSirtuin functions and modulation: from chemistry to the clinic
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“Their bestcharacterized activity is NAD-dependent lysine deacetylation, but recent studies demonstrated that some SIRTs also remove other acyl groups such as succinyl, malonyl, glutaryl, and long-chain fatty acyl groups [2, 3] (Table 1).”
BackgroundThe Application of Deep Learning in Cancer Prognosis Prediction
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“SIRT7 directly binds L1 elements and promotes L1 sequences association with the nuclear lamina protein (Lamin A/C) by deacetylating H3K18 (Van Meter et al., 2014; Vazquez et al., 2019).”
BackgroundInfluentialSIRT5 regulation of ammonia-induced autophagy and mitophagy
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SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion
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“Furthermore, SIRT4 showed no deacylation activity against known dicarboxyl-acyl modifications (Peng et al., 2011; Tan et al., 2014) and does not efficiently remove long-chain acyl modifications (Feldman et al., 2013; Madsen et al., 2016).”
BackgroundMethodInfluentialSelf-citationProtein acetylation in metabolism – metabolites and cofactors
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BackgroundInfluentialRewiring urea cycle metabolism in cancer to support anabolism
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Nonenzymatic Protein Acylation as a Carbon Stress Regulated by Sirtuin Deacylases
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“Recently, SIRT5 was shown to have robust lysine desuccinylase and demalonylase activities, expanding the known enzymatic activities of the sirtuin family (Du et al., 2011; Peng et al., 2011).”
InfluentialSelf-citationMechanisms and Dynamics of Protein Acetylation in Mitochondria
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“Acetylation, succinylation [99], propionylation [100], butyrylation [50,101], malonylation [29], glutarylation [28], myristoylation [102], and crotonylation [103] are among lysine modifications previously discovered.”
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SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense
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“The potential presence of a transferase for lysine succinylation, malonylation, or glutarylation has not been identified yet, and investigation on the regulation of these three acidic lysine modifications has mainly been focusing on the deacylase sirtuin 5 (SIRT5) [10,21].”
Sirtuins: guardians of mammalian healthspan
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Self-citationSIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer
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“…have emerged as functionally important modifications, but most likely have distinct functions from Kac in regulating metabolism and other cellular processes (Park et al. 2013; Rardin et al. 2013; Tan et al. 2014; Nishida et al. 2015; Sadhukhan et al. 2016; Hershberger, Abraham, et al. 2017).”
BackgroundInfluentialSelf-citationCompartmentalised acyl-CoA metabolism and roles in chromatin regulation
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“Increased total protein glutarylation was observed in mammalian cells deficient in GCDH, the FAD-dependent enzyme that converts glutaryl-CoA to crotonoyl-CoA, as well as in Drosophila fed increasing amounts of tryptophan [158].”
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“…acylations in core histones, including lysine propionylation, butyrylation, 2-hydroxyisobutyrylation, crotonylation, malonylation, succinylation, and glutarylation (Chen This is an open access article under the CC BY-N et al., 2007; Dai et al., 2014; Tan et al., 2011, 2014; Xie et al., 2012).”
BackgroundSelf-citationA Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation
Wagner, G. R., Bhatt, D. P., O’Connell, T. M., Thompson, J. W., Dubois, L. G., Backos, D. S., Yang, H., Mitchell, G. A., Ilkayeva, O. R., Stevens, R. D., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.006 · Cited by 258
“…anhydrides at physiological pH and temperature, and have corresponding, validated PTMsassociatedwith them (lysine succinylation and glutarylation; Tan et al., 2014; Zhang et al., 2011), we considered the possibility that other endogenous four- and fivecarbon backbone dicarboxylacyl-CoAs might…”
InfluentialSelf-citationSENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism
Wang, T., Cao, Y., Zheng, Q., Tu, J., Zhou, W., He, J., Zhong, J., Chen, Y., Wang, J., Cai, R., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.06.008 · Cited by 250
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Cellular metabolism regulates the differentiation and function of T-cell subsets
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SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation
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Characterization of histone acylations links chromatin modifications with metabolism
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“, 2012) with a dedicated, carboxyl-specific deacetylase, SIRT5 (Du et al., 2011; Park et al., 2013; Peng et al., 2011; Tan et al., 2014).”
BackgroundSuccinylation Links Metabolism to Protein Functions
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Lysine benzoylation is a histone mark regulated by SIRT2
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Self-citationPLMD: An updated data resource of protein lysine modifications
Xu, H., Zhou, J., Lin, S., Deng, W., Zhang, Y. W., & Xue, Y. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.03.007 · Cited by 220
“Ub-UbLs, ubiquitin and ubiquitin-like modificat succinylation, malonylation, propionylation crotonylation, glutarylation, and 2-hydroxyisobutyrylation, which has greatly advanced the identification and functional investigation of these PLMs (Chen et al., 2007; Xie et al., 2012; Dai et al., 2014; Tan et al., 2014).”
InfluentialSelf-citationRole of NAD+ and mitochondrial sirtuins in cardiac and renal diseases
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Self-citationCrossing epigenetic frontiers: the intersection of novel histone modifications and diseases
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“121 Succ can exert a direct in fl uence on the organization of chromatin by chemically altering histones or by modulating interactions within the nucleus.”
BackgroundMalonylation of GAPDH is an inflammatory signal in macrophages
Galván-Peña, S., Carroll, R. G., Newman, C. F., Hinchy, E. C., Pålsson‐McDermott, E. M., Robinson, E. K., Covarrubias, S., Nadin, A. J., James, A. M., Haneklaus, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08187-6 · Cited by 220
Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation
Wang, G., Meyer, J. G., Cai, W., Softic, S., Li, M. E., Verdin, E. M., Newgard, C. B., Schilling, B., & Kahn, C. R. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.03.021 · Cited by 216
“, 2013), and deglutarylates carbamoyl-phosphate synthase 1 (CPS1) to enhance its activity (Tan et al., 2014).”
BackgroundInfluentialModification of Proteins by Metabolites in Immunity
Diskin, C., Ryan, T. A. J., & O'Neill, L. A. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.09.014 · Cited by 215
Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio
Anderson, K. A., Madsen, A. S., Olsen, C. A., & Hirschey, M. D. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.09.005 · Cited by 217
“We also found that NADH inhibits both SIRT1-mediated deacetylase and SIRT5mediated desuccinylase activities via a non-competitive mechanism for both peptide substrate and NAD+ [50].”
MethodInfluentialSelf-citationBeyond histone acetylation—writing and erasing histone acylations
Zhao, S., Zhang, X., & Li, H. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.10.001 · Cited by 215
The role of mitochondrial dysfunction in age-related diseases
Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205
“t1:9 Deglutarylation SIRT5 CPS1, HADHA, GOT2 [174] t1:10 ADP ribosylation SIRT4 GDH [172] t1:11 Sumoylation MULAN, SENP2 Drp1 [173,175]”
The Chemical Biology of Reversible Lysine Post-translational Modifications
Wang, Z. A., & Cole, P. A. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.002 · Cited by 216
Deposition of 5-Methylcytosine on Enhancer RNAs Enables the Coactivator Function of PGC-1α
Aguiló, F., Li, S., Balasubramaniyan, N., Sancho, A., Benko, S., Zhang, F., Vashisht, A. A., Rengasamy, M., Andino, B., Chen, C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.043 · Cited by 205
“To further evaluate the physiological function of Sirt5 eRNA, we tested the lysine deglutarylase activity of SIRT5 upon knockdown of its associated eRNA (Tan et al., 2014).”
BackgroundLi, W., Li, F., Zhang, X., Lin, H., & Xu, C. S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00825-8 · Cited by 211
“Carbamoyl phosphate synthetase 1 (CPS1), the key enzyme important for ammoniadetoxifying urea cycle, was identified to be a glutarylated substrate with inhibit enzyme activity after glutarylation.(63,65) Other than MS, the novel bioinformatics tools, the biased support vector machine algorithm, and machine-learning sc…”
BackgroundInfluentialMoonlighting functions of metabolic enzymes and metabolites in cancer
Pan, C., Li, B., & Simon, M. C. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.031 · Cited by 198
Colak, G., Pougovkina, O., Dai, L., Tan, M., Brinke, H. T., Huang, H., Cheng, Z., Park, J.-S., Wan, X., Liu, X., et al. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.048850 · Cited by 187
“the widely studied lysine acetylation pathway (10, 11).”
BackgroundResultSelf-citationFeldman, J. L., Dittenhafer‐Reed, K. E., Kudo, N., Thelen, J. N., Ito, A., Yoshida, M., & Denu, J. M. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00150 · Cited by 191
Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis
Sun, R., Zhang, Z., Bao, R., Guo, X., Gu, Y., Yang, W., Wei, J., Chen, X., Tong, L., Meng, J., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.02.030 · Cited by 189
NAMPT-Mediated NAD+ Biosynthesis Is Essential for Vision In Mice
Lin, J. B., Kubota, S., Ban, N., Yoshida, M., Santeford, A. C., Sène, A., Nakamura, R. E. I., Zapata, N., Kubota, M., Tsubota, K., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.073 · Cited by 189
“…et al., 2015) and SIRT5 regulates predominantly protein succinylation, malonylation, and glutarylation (Du et al., 2011; Nishida et al., 2015; Papanicolaou et al., 2014; Tan et al., 2014), we tested whether NAMPT inhibition modulates the acylation of mitochondrial proteins in photoreceptor cells.”
Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype
Carafa, V., Altucci, L., & Nebbioso, A. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00038 · Cited by 186
“Another activity described for SIRT5 is glutarylation, which involves the removal of glutaryl-CoA, a metabolite of amino acid metabolism, structurally similar to succinyl-CoA and malonyl-CoA (Tan et al., 2014).”
BackgroundShort-chain fatty acid, acylation and cardiovascular diseases
Chen, X., Chen, X., & Tang, X. (2020) · Clinical Science · doi:10.1042/cs20200128 · Cited by 189
Metabolites Regulate Cell Signaling and Growth via Covalent Modification of Proteins
Figlia, G., Willnow, P., & Teleman, A. A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.036 · Cited by 185
Christensen, D. G., Xie, X., Basisty, N., Byrnes, J., McSweeney, S. M., Schilling, B., & Wolfe, A. J. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01604 · Cited by 184
“…(Tan et al., 2011; Sabari et al., 2015), succinylation (Zhang et al., 2011), malonylation (Du et al., 2011; Peng et al., 2011), glutarylation (Tan et al., 2014), 2-hydroxyisobutyrylation (Dai et al., 2014), pupylation (Becker and Darwin, 2017), and Nε-lysine acetylation, which is becoming…”
BackgroundCharacterization of the cardiac succinylome and its role in ischemia–reperfusion injury
Boylston, J. A., Sun, J., Chen, Y., Guček, M., Sack, M. N., & Murphy, E. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.09.005 · Cited by 181
Self-citationThe role of mitochondrial sirtuins in health and disease
Osborne, B., Bentley, N. L., Montgomery, M. K., & Turner, N. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.197 · Cited by 183
Structure of p300 in complex with acyl-CoA variants
Kaczmarska, Z., Ortega, E. M., Goudarzi, A., Huang, H., KIM, S. ‐., Márquez, J. A., Zhao, Y., Khochbin, S., & Panne, D. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2217 · Cited by 186
Self-citationWang, Y.-Q., Wang, H.-L., Xu, J., Tan, J., Fu, L., Wang, J., Zou, T., Sun, D., Gao, Q., Chen, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02951-4 · Cited by 169
Self-citationGlutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics
Bao, X., Liu, Z., Zhang, W., Gladysz, K., Fung, Y. M. E., Tian, G., Xiong, Y., Wong, J. W. H., Yuen, K. W. Y., & Li, X. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.018 · Cited by 171
Acetylation of Mitochondrial Proteins in the Heart: The Role of SIRT3
Parodi‐Rullán, R. M., Chapa‐Dubocq, X. R., & Javadov, S. A. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01094 · Cited by 168
“It has also been reported that SIRT5 can function as a deglutarylate (Tan et al., 2014).”
BackgroundFeatures and regulation of non-enzymatic post-translational modifications
Harmel, R. K., & Fiedler, D. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2575 · Cited by 171
Understanding the Function of Mammalian Sirtuins and Protein Lysine Acylation
Wang, M., & Lin, H. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-082520-125411 · Cited by 174
Sirtuins and their Biological Relevance in Aging and Age-Related Diseases
Zhao, L., Cao, J., Hu, K., He, X., Dou, Y., Tong, T., & Han, L. (2020) · Aging and Disease · doi:10.14336/ad.2019.0820 · Cited by 178
“studies have suggested that sirt5 can mediate protein desuccinylation, demalonylation, and deglutarylation [21, 37, 38].”
BackgroundMitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer
Kumar, S., & Lombard, D. B. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6213 · Cited by 160
“identified and validated lysine glutarylation as an evolutionary conserved posttranslational modification; similar to lysine succinylation, this modification was also regulated by SIRT5 (156).”
InfluentialSelf-citationSIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
Guo, Z., Li, P., Ge, J., & Li, H. (2022) · Aging and Disease · doi:10.14336/ad.2022.0413 · Cited by 166
“In addition, a long active site is found between the Rossmann and Zn subdomains of SIRT6; it is the widest hydrophobic channel pocket in sirtuins [12], which may explain the reason that SIRT6 prefers long-chain fatty acylation to acetylation, at least in vitro [15-17] (Fig.”
BackgroundDiscovering the landscape of protein modifications
Keenan, E. K., Zachman, D. K., & Hirschey, M. D. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.015 · Cited by 160
Self-citationAdvances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond
Sun, Q., Karwi, Q. G., Wong, N. K. P., & Lopaschuk, G. D. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae231 · Cited by 164
Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions
Weinert, B. T., Moustafa, T., Iešmantavičius, V., Zechner, R., & Choudhary, C. (2015) · The EMBO Journal · doi:10.15252/embj.201591271 · Cited by 150
“…sirtuin deacylase SIRT5 suppresses both succinylation and glutarylation in mitochondria (Du et al , 2011; Park et al , 2013; Rardin et al , 2013a; Tan et al , 2014), and both of these modifications may occur nonenzymatically (Wagner & Payne, 2013; Weinert et al , 2013b; Tan et al , 2014),…”
Smestad, J. A., Erber, L. N., Chen, Y., & Maher, L. J. (2018) · iScience · doi:10.1016/j.isci.2018.03.012 · Cited by 159
“…others including acetylation, propionylation, malonylation, crotonylation, butyrylation, glutarylation, 2-hydroxyisobutyrylation, and β-hydroxybutyrylation (Chen et al., 2007; Choudhary et al., 2009; Dai et al., 2014; Du et al., 2011; Garrity et al., 2007; Tan et al., 2011, 2014; Xie et al., 2016).”
Self-citationPost-translational modifications in mitochondria: protein signaling in the powerhouse
Stram, A. R., & Payne, R. M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2280-4 · Cited by 149
“Taken together, lysine acylation in its early stages of characterization appears to regulate diverse mitochondrial metabolic processes through protein post-translational processing [121].”
p53 β-hydroxybutyrylation attenuates p53 activity
Liu, K., Li, F., Sun, Q., Lin, N., Han, H., You, K., Tian, F., Mao, Z., Li, T., Tong, T., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1463-y · Cited by 156
Self-citationLandscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway
Huang, H., Luo, Z., Qi, S., Huang, J. L., Xu, P., Wang, X., Gao, L. P., Li, F., Wang, J., Zhao, W., et al. (2017) · Cell Research · doi:10.1038/cr.2017.149 · Cited by 154
Self-citationCommon errors in mass spectrometry‐based analysis of post‐translational modifications
Kim, M., Zhong, J., & Pandey, A. (2015) · PROTEOMICS · doi:10.1002/pmic.201500355 · Cited by 155
Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI
Chiba, T., Peasley, K., Cargill, K. R., Maringer, K. V., Bharathi, S. S., Mukherjee, E., Zhang, Y., Holtz, A. N., Basisty, N., Yagobian, S. D., et al. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019020163 · Cited by 143
Self-citationKetogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation
Koronowski, K. B., Greco, C. M., Huang, H., Kim, J., Fribourgh, J. L., Crosby, P., Mathur, L., Ren, X., Partch, C. L., Jang, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109487 · Cited by 144
“For example, CPS1, a rate-limiting enzyme in the urea cycle, is modified at 35 sites, including lysine residues previously linked to posttranslational control of its activity (Tan et al., 2014).”
BackgroundSelf-citationLactylation: a Passing Fad or the Future of Posttranslational Modification
Qi, X., Wang, H., Li, Q., Liu, S., Qu, K., Liu, C., & Zhang, J. (2022) · Inflammation · doi:10.1007/s10753-022-01637-w · Cited by 150
Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.04.007 · Cited by 149
Self-citationThe chemical biology of sirtuins
Chen, B., Zang, W., Wang, J., Huang, Y., He, Y., Yan, L., Liu, J., & Zheng, W. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00373j · Cited by 146
CPT 1A‐mediated succinylation of S100A10 increases human gastric cancer invasion
Wang, C., Zhang, C., Li, X., Shen, J., Xu, Y., Shi, H. M., Mu, X., Pan, J., Zhao, T., Li, M., et al. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13920 · Cited by 141
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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