Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity

Mathias, Rommel A.; Greco, Todd M.; Oberstein, Adam; Budayeva, Hanna G.; Chakrabarti, Rumela; Rowland, Elizabeth A.; Kang, Yibin; Shenk, Thomas; Cristea, Ileana M.

doi:10.1016/j.cell.2014.11.046

Cited by 434Sirtuins and Resveratrol in MedicineBiochemical Acid Research StudiesMetabolism, Diabetes, and Cancer

Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity

Open access

Mathias, Rommel A., Greco, Todd M., Oberstein, Adam, Budayeva, Hanna G., Chakrabarti, Rumela, Rowland, Elizabeth A., Kang, Yibin, Shenk, Thomas +1 more·2014·Cell

DOI 10.1016/j.cell.2014.11.046PMC PMC4344121

Open this paper in CoChat — free account Open PDF

Abstract

Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellular lipoamidase that regulates the pyruvate dehydrogenase complex (PDH). Importantly, SIRT4 catalytic efficiency for lipoyl- and biotinyl-lysine modifications is superior to its deacetylation activity. PDH, which converts pyruvate to acetyl-CoA, has been known to be primarily regulated by phosphorylation of its E1 component. We determine that SIRT4 enzymatically hydrolyzes the lipoamide cofactors from the E2 component dihydrolipoyllysine acetyltransferase (DLAT), diminishing PDH activity. We demonstrate SIRT4-mediated regulation of DLAT lipoyl levels and PDH activity in cells and in vivo, in mouse liver. Furthermore, metabolic flux switching via glutamine stimulation induces SIRT4 lipoamidase activity to inhibit PDH, highlighting SIRT4 as a guardian of cellular metabolism.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2014.11.046

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

SIRT4 can regulate lipoyl- and biotinyl-lysine modifications and demethylglutarylate branched-chain acyl-lysines.
“One study has shown that SIRT4 can regulate the levels of both lipoyl- and biotinyl-lysine modifications in pyruvate dehydrogenase and likely other proteins ((Mathias et al. 2014)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Mathias et al. 2014
Lipoylation occurs at two sites in the E2 N-terminal region, K132 and K259 in the human sequence, and is enzymatically reversed by SIRT4.
“Lipoylation occurs at two sites in the E2 N-terminal region (K132 and K259 in the human sequence), and is enzymatically reversed by SIRT4 ((Mathias et al. 2014)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Mathias et al. 2014
SIRT4 delipoylation activity suggests potential inhibitory delipoylation of the downstream oxoglutarate dehydrogenase complex.
“SIRT4’s delipoylation activity ((Mathias et al. 2014)) also suggests the potential for inhibitory delipoylation of the downstream oxoglutarate dehydrogenase complex, which functions similarly to pyruvate dehydrogenase (discussed above).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Mathias et al. 2014
SIRT4 cleaves Klip and Kmgc; SIRT5 regulates Kmal, Ksuc, and Kglu; SIRT2 and SIRT6 efficiently cleave Kmyr.
“For example, SIRT4 has been shown to cleave e -N -lipoyllysine (Klip) (Mathias et al., 2014) and e -N -(3-methylglutaconyl)lysine (Kmgc) (Anderson et al., 2017), SIRT5 regulates e -N -malonyllysine (Kmal) (Du et al., 2011; Peng et al., 2011; Hirschey and Zhao, 2015; Nishida et al., 2015), e -N -succinyllysine (Ksuc) (Du et al., 2011; Park et al., 2013; Rardin et al., 2013; Hirschey and Zhao, 2015)”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Mathias et al., 2014

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
ProteomeXchange provides globally coordinated proteomics data submission and dissemination
Vizcaíno, J. A., Deutsch, E. W., Wang, R., Csordás, A., Reisinger, F., Ríos, D., Dianes, J. A., Sun, Z., Farrah, T., Bandeira, N., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2839 · Cited by 2,735 · see citing works
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429 · see citing works
Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins
Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0033 · Cited by 1,364 · see citing works
Proteomic Mapping of Mitochondria in Living Cells via Spatially Restricted Enzymatic Tagging
Martell, J. D., Ting, A. Y., Rhee, H., Zou, P., Udeshi, N. D., Mootha, V. K., & Carr, S. A. (2012) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 1,330 · see citing works
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216 · see citing works
SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic β Cells
Haigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · see citing works
Lysine glutarylation is a protein posttranslational modification regulated by SIRT5
Tan, M., Peng, C., Anderson, K. A., Chhoy, P., Xie, Z., Dai, L., Park, J., Chen, Y., Huang, H., Zhang, Y., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.014 · Cited by 844 · see citing works
Characterization of Five Human cDNAs with Homology to the Yeast SIR2 Gene: Sir2-like Proteins (Sirtuins) Metabolize NAD and May Have Protein ADP-Ribosyltransferase Activity
Frye, R. A. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0897 · Cited by 809 · see citing works
SAINT: probabilistic scoring of affinity purification–mass spectrometry data
Choi, H., Larsen, B., Lin, Z.-Y., Breitkreutz, A., Mellacheruvu, D., Fermin, D., Qin, Z. S., Tyers, M., Gingras, A.-C., & Nesvizhskii, A. I. (2011) · Nature Methods · doi:10.1038/nmeth.1541 · Cited by 800 · see citing works
The first identification of lysine malonylation substrates and its regulatory enzyme
Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012658 · Cited by 751 · see citing works
Sir2 links chromatin silencing, metabolism, and agingPreprint
Guarente, L. (2000) · Genes & Development · doi:10.1101/gad.14.9.1021 · Cited by 718 · see citing works
SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks
Rardin, M. J., He, W., Nishida, Y., Newman, J. C., Carrico, C., Danielson, S. R., Guo, A., Gut, P., Sahu, A. K., Li, B., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.013 · Cited by 711 · see citing works
SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine
Jiang, H., Khan, S., Wang, Y., Charron, G., He, B., Sebastian, C., Du, J., Kim, R., Ge, E., Mostoslavsky, R., et al. (2013) · Nature · doi:10.1038/nature12038 · Cited by 697 · see citing works
α-KETO ACID DEHYDROGENASE COMPLEXES, X. REGULATION OF THE ACTIVITY OF THE PYRUVATE DEHYDROGENASE COMPLEX FROM BEEF KIDNEY MITOCHONDRIA BY PHOSPHORYLATION AND DEPHOSPHORYLATION
Linn, T. C., Pettit, F. H., & Reed, L. J. (1969) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.62.1.234 · Cited by 671 · see citing works
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
Verdin, E., Hirschey, M. D., Finley, L. W. S., & Haigis, M. C. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.003 · Cited by 661 · see citing works
Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins
Feldman, J. L., Baeza, J., & Denu, J. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.511261 · Cited by 637 · cited 4× · see citing works
“, 2013) and by screening the activity of recombinant SIRTs against various acyl-histone peptides (Feldman et al., 2013).”
BackgroundMethodInfluential
The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4
Csibi, A., Fendt, S.-M., Li, C., Poulogiannis, G., Choo, A. Y., Chapski, D. J., Jeong, S. M., Dempsey, J. M., Parkhitko, A., Morrison, T., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.023 · Cited by 586 · see citing works
METABOLIC COUPLING FACTORS IN PANCREATIC β-CELL SIGNAL TRANSDUCTION
Newgard, C. B., & McGarry, J. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003353 · Cited by 531 · see citing works
SIRT4 Has Tumor-Suppressive Activity and Regulates the Cellular Metabolic Response to DNA Damage by Inhibiting Mitochondrial Glutamine Metabolism
Jeong, S. M., Xiao, C., Finley, L. W. S., Lahusen, T., Souza, A. L., Pierce, K., Li, Y.-H., Wang, X., Laurent, G., German, N. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.024 · Cited by 445 · see citing works
Domains, motifs, and linkers in 2-oxo acid dehydrogenase multienzyme complexes: a paradigm in the design of a multifunctional protein
Perham, R. N. (1991) · Biochemistry · doi:10.1021/bi00099a001 · Cited by 422 · see citing works
Regulation of Insulin Secretion by SIRT4, a Mitochondrial ADP-ribosyltransferase
Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B. J., Castronovo, V., Maechler, P., & Verdin, E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705488200 · Cited by 422 · see citing works
SIRT4 Coordinates the Balance between Lipid Synthesis and Catabolism by Repressing Malonyl CoA Decarboxylase
Laurent, G., German, N. J., Saha, A. K., de Boer, V. C. J., Davies, M. N., Koves, T. R., Dephoure, N., Fischer, F. F., Boanca, G., Vaitheesvaran, B., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.05.012 · Cited by 394 · see citing works
SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells
Nasrin, N., Wu, X.-P., Fortier, E., Feng, Y., Bare, O., Chen, S., Ren, X., Wu, Z., Streeper, R. S., & Bordone, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.124164 · Cited by 323 · see citing works
Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex
Fan, J., Shan, C., Kang, H.-B., Elf, S., Xie, J., Tucker, M., Gu, T.-L., Aguiar, M., Lonning, S., Chen, H., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.026 · Cited by 305 · see citing works
Self-citation
The functional interactome landscape of the human histone deacetylase family
Joshi, P., Greco, T. M., Guise, A. J., Luo, Y., Yu, F., Nesvizhskii, A. I., & Cristea, I. M. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.26 · Cited by 289 · see citing works
Self-citation
Modular Stop and Go Extraction Tips with Stacked Disks for Parallel and Multidimensional Peptide Fractionation in Proteomics
Ishihama, Y., Rappsilber, J., & Mann, M. (2006) · Journal of Proteome Research · doi:10.1021/pr050385q · Cited by 285 · see citing works
Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation
Jing, E., O’Neill, B. T., Rardin, M. J., Kleinridders, A., Ilkeyeva, O. R., Ussar, S., Bain, J. R., Lee, K. Y., Verdin, E. M., Newgard, C. B., et al. (2013) · Diabetes · doi:10.2337/db12-1650 · Cited by 283 · see citing works
Structural Basis of Inhibition of the Human NAD+-Dependent Deacetylase SIRT5 by Suramin
Schuetz, A., Min, J., Antoshenko, T., Wang, C.-L., Allali‐Hassani, A., Dong, A., Loppnau, P., Vedadi, M., Bochkarev, A. V., Sternglanz, R., et al. (2007) · Structure · doi:10.1016/j.str.2007.02.002 · Cited by 264 · see citing works
Fluorescent Proteins as Proteomic Probes
Cristea, I. M., Williams, R., Chait, B. T., & Rout, M. P. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500227-mcp200 · Cited by 251 · see citing works
Self-citation
The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes
Zhou, Z., McCarthy, D. B., O'Connor, C. M., Reed, L. J., & Stoops, J. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.011597698 · Cited by 238 · see citing works
Protein Lysine Acylation and Cysteine Succination by Intermediates of Energy Metabolism
Lin, H., Su, X., & He, B. (2012) · ACS Chemical Biology · doi:10.1021/cb3001793 · Cited by 236 · see citing works
Mitochondrial Protein Acylation and Intermediary Metabolism: Regulation by Sirtuins and Implications for Metabolic Disease
Newman, J. C., He, W., & Verdin, E. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.404863 · Cited by 207 · see citing works
An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms
Rauh, D., Fischer, F. F., Gertz, M., Lakshminarasimhan, M., Bergbrede, T., Aladini, F., Kambach, C., Becker, C. F. W., Zerweck, J., Schutkowski, M., et al. (2013) · Nature Communications · doi:10.1038/ncomms3327 · Cited by 204 · see citing works
Functional Proteomics Establishes the Interaction of SIRT7 with Chromatin Remodeling Complexes and Expands Its Role in Regulation of RNA Polymerase I Transcription
Tsai, Y.-C., Greco, T. M., Boonmee, A., Miteva, Y., & Cristea, I. M. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.a111.015156 · Cited by 198 · see citing works
Self-citation
SIRT4 Represses Peroxisome Proliferator-Activated Receptor α Activity To Suppress Hepatic Fat Oxidation
Laurent, G., de Boer, V. C. J., Finley, L. W. S., Sweeney, M. O., Lu, H., Schug, T. T., Cen, Y., Jeong, S. M., Li, X., Sauve, A. A., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00087-13 · Cited by 154 · see citing works
Monitoring phosphorylation of the pyruvate dehydrogenase complex
Rardin, M. J., Wiley, S. E., Naviaux, R. K., Murphy, A. N., & Dixon, J. E. (2009) · Analytical Biochemistry · doi:10.1016/j.ab.2009.03.040 · Cited by 152 · see citing works
Dihydrolipoamide Dehydrogenase-binding Protein of the Human Pyruvate Dehydrogenase Complex
Harris, R. A., Bowker-Kinley, M. M., Wu, P., Jeng, J., & Popov, K. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.19746 · Cited by 110 · see citing works
Structural Insight into Interactions between Dihydrolipoamide Dehydrogenase (E3) and E3 Binding Protein of Human Pyruvate Dehydrogenase Complex
Brautigam, C. A., Wynn, R., Chuang, J. L., Machius, M., Tomchick, D. R., & Chuang, D. (2006) · Structure · doi:10.1016/j.str.2006.01.001 · Cited by 105 · see citing works
Sir2 Protein Deacetylases: Evidence for Chemical Intermediates and Functions of a Conserved Histidine
Smith, B. C., & Denu, J. M. (2005) · Biochemistry · doi:10.1021/bi052014t · Cited by 101 · see citing works
ATP‐dependent inactivation of heart muscle pyruvate dehydrogenase and reactivation by Mg++
WIELAND, O. H., & JAGOW-WESTERMANN, B. (1969) · FEBS Letters · doi:10.1016/0014-5793(69)80156-0 · Cited by 94 · see citing works
Proteomic Mapping of Mitochondria in Living Cells via Spatially Restricted Enzymatic Tagging
Rhee, H.-W., Zou, P., Udeshi, N. D., Martell, J. D., Mootha, V. K., Carr, S. A., & Ting, A. Y. (2013) · Science · doi:10.1126/science.1230593 · Cited by 83 · see citing works
SIRT3 and SIRT4 are mitochondrial tumor suppressor proteins that connect mitochondrial metabolism and carcinogenesis
Zhu, Y., Yan, Y., Principe, D. R., Zou, X., Vassilopoulos, A., & Gius, D. R. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-15 · Cited by 76 · see citing works
Label-Free Quantitation of Protein Modifications by Pseudo Selected Reaction Monitoring with Internal Reference Peptides
Sherrod, S. D., Myers, M. V., Li, M., Myers, J. S., Carpenter, K. L., MacLean, B., MacCoss, M. J., Liebler, D. C., & Ham, A. L. (2012) · Journal of Proteome Research · doi:10.1021/pr201240a · Cited by 68 · see citing works
Changes in the core of the mammalian-pyruvate dehydrogenase complex upon selective removal of the lipoyl domain from the transacetylase component but not from the protein X component.
Rahmatullah, M., Radke, G. A., Andrews, P., & Roche, T. E. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77332-8 · Cited by 56 · see citing works
Critical Role of a Lipoyl Cofactor of the Dihydrolipoyl Acetyltransferase in the Binding and Enhanced Function of the Pyruvate Dehydrogenase Kinase
Radke, G. A., Ono, K., Ravindran, S., & Roche, T. E. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1146 · Cited by 41 · see citing works
Inhibition of Pyruvate Dehydrogenase during the Metabolism of Glutamine and Proline in Hemoglobin‐Free Perfused Rat Liver
Häussinger, D., Gerok, W., & Sies, H. (1982) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1982.tb06747.x · Cited by 23 · see citing works
Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases
Wirth, M., Karaca, S., Wenzel, D., Ho, L., Tishkoff, D. X., Lombard, D. B., Verdin, E. M., Urlaub, H., Jedrusik, M. A., & Fischle, W. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.02.002 · Cited by 22 · see citing works
Liberation of lipoate by human serum lipoamidase from bovine heart pyruvate dehydrogenase
Oizumi, J., & Hayakawa, K. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92361-9 · Cited by 19 · see citing works
Sizing of bovine heart and kidney pyruvate dehydrogenase complex and dihydrolipoyl transacetylase core by quasielastic light scattering
Roche, T. E., POWERS‐GREENWOOD, S. L., Shi, W., Zhang, W. B., Ren, S. Z., Roche, E. D., Cox, D. J., & SORENSEN, C. M. (1993) · Biochemistry · doi:10.1021/bi00072a019 · Cited by 15 · see citing works
Co-purification of human serum lipoamidase and biotinidase: evidence that the two enzyme activities are due to the same enzyme protein
Nilsson, L. J., & Kågedal, B. (1993) · Biochemical Journal · doi:10.1042/bj2910545 · Cited by 15 · see citing works
Lipoamidase and biotinidase deficiency: evidence that lipoamidase and biotinidase are the same enzyme in human serum.
Nilsson, L., & Ronge, E. (1992) · PubMed · Cited by 15 · see citing works

Flagged first, then by citations

Sorted by citations

NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441 · see citing works
Mitochondrial dysfunction: mechanisms and advances in therapy
Yao, Z., Li, H., Liao, P., Chen, L., Pan, Y., Zheng, Y., Zhang, C., Liu, D., Zheng, M., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01839-8 · Cited by 1,274 · see citing works
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,076 · see citing works
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 975 · see citing works
The world of protein acetylation
Drazic, A., Myklebust, L. M., Ree, R., & Arnesen, T. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.06.007 · Cited by 798 · see citing works
The multifaceted functions of sirtuins in cancer
Chalkiadaki, A., & Guarente, L. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3985 · Cited by 501 · see citing works
Lipoic acid metabolism and mitochondrial redox regulation
Solmonson, A., & DeBerardinis, R. J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000259 · Cited by 492 · see citing works
Sirtuin activators and inhibitors: Promises, achievements, and challenges
Dai, H., Sinclair, D. A., Ellis, J. L., & Steegborn, C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.03.004 · Cited by 463 · see citing works
“There is a growing list of chemical reactions that the mammalian sirtuins catalyze, including demalonylation, desuccinylation, decrotonylation, depropyonylation, delipoamidation, other long-chain fatty acid deacylations, which are generally referred to as “deacylation reactions”, and mono-ADP-ribosylation, which is di…”
Background
Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer
Stacpoole, P. W. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx071 · Cited by 408 · see citing works
The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy
Guo, L., Tian, Y., & Zhu, W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.576946 · Cited by 358 · see citing works
Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in Response to Membrane Depolarization
Yang, W., Nagasawa, K., Münch, C., Xu, Y., Satterstrom, F. K., Jeong, S., Hayes, S., Jedrychowski, M. P., Vyas, F. S., Zaganjor, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.016 · Cited by 341 · see citing works
SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion
Anderson, K. A., Huynh, F. K., Fisher-Wellman, K., Stuart, J. D., Peterson, B. S., Douros, J. D., Wagner, G. R., Thompson, J. W., Madsen, A. S., Green, M. F., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.003 · Cited by 326 · see citing works
Effects of Oxidative Stress on Mesenchymal Stem Cell Biology
Denu, R. A., & Hematti, P. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/2989076 · Cited by 331 · see citing works
Protein acetylation in metabolism – metabolites and cofactors
Menzies, K. J., Zhang, H., Katsyuba, E., & Auwerx, J. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.181 · Cited by 331 · see citing works
The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications
Carrico, C., Meyer, J. G., He, W., Gibson, B. W., & Verdin, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.016 · Cited by 331 · see citing works
Mechanisms and Dynamics of Protein Acetylation in Mitochondria
Baeza, J., Smallegan, M. J., & Denu, J. M. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.006 · Cited by 312 · see citing works
Mitochondrial Sirtuins and Molecular Mechanisms of Aging
van de Ven, R. A. H., Santos, D., & Haigis, M. C. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.02.005 · Cited by 309 · see citing works
Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility
Tatone, C., Emidio, G. D., Barbonetti, A., Carta, G., Luciano, A. M., Falone, S., & Amicarelli, F. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy003 · Cited by 294 · see citing works
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Kumar, S., & Lombard, D. B. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1458071 · Cited by 264 · see citing works
Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease
Rowland, E. A., Snowden, C. K., & Cristea, I. M. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.11.003 · Cited by 257 · see citing works
Self-citation
SENP1-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 · see citing works
The Substrate Specificity of Sirtuins
Bheda, P., Jing, H., Wolberger, C., & Lin, H. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014537 · Cited by 247 · see citing works
Mitochondrial sirtuins, metabolism, and aging
Ji, Z., Liu, G., & Qu, J. T. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.11.005 · Cited by 246 · see citing works
Sirtuin regulation in aging and injury
Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236 · see citing works
SIRT6, a Mammalian Deacylase with Multitasking Abilities
Chang, A. R., Ferrer, C. M., & Mostoslavsky, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00030.2018 · Cited by 236 · see citing works
Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases
Hershberger, K. A., Martin, A. S., & Hirschey, M. D. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.5 · Cited by 218 · see citing works
Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome
Fluge, Ø., Mella, O., Bruland, O., Risa, K., Dyrstad, S. E., Alme, K., Rekeland, I. G., Sapkota, D., Røsland, G. V., Fosså, A., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.89376 · Cited by 209 · see citing works
An overview of Sirtuins as potential therapeutic target: Structure, function and modulators
Wang, Y., He, J., Liao, M., Hu, M., Li, W., Ouyang, H., Wang, X., Ye, T., Zhang, Y., & Ouyang, L. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.028 · Cited by 206 · see citing works
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 · see citing works
The Role of Sirtuins in Cellular Homeostasis
Kupis, W., Pałyga, J., Tomal, E., & Niewiadomska, E. (2016) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-016-0492-6 · Cited by 200 · see citing works
Sirtuins in metabolism, DNA repair and cancer
Mei, Z., Zhang, X., Yi, J., Huang, J., He, J., & Tao, Y. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0461-5 · Cited by 191 · see citing works
Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Park, S., Jeon, J., Min, B.-K., Ha, C., Thoudam, T., Park, B.-Y., & Lee, I. (2018) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2018.0101 · Cited by 186 · see citing works
The 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 179 · see citing works
Two-stage metabolic remodelling in macrophages in response to lipopolysaccharide and interferon-γ stimulation
Seim, G. L., Britt, E. C., John, S. V., Yeo, F. J., Johnson, A. R., Eisenstein, R. S., Pagliarini, D. J., & Fan, J. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0083-2 · Cited by 174 · see citing works
SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy
Lang, A., Anand, R., Altinoluk-Hambüchen, S., Ezzahoini, H., Stefanski, A., Iram, A., Bergmann, L., Urbach, J., Böhler, P., Hänsel, J., et al. (2017) · Aging · doi:10.18632/aging.101307 · Cited by 145 · see citing works
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 · see citing works
Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy
Ganesan, R., Hos, N. J., Gutiérrez, S., Fischer, J., Stepek, J. M., Daglidu, E., Krönke, M., & Robinson, N. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006227 · Cited by 142 · see citing works
Emerging Roles for SIRT5 in Metabolism and Cancer
Bringman, L. R., Guo, A. H., Lyssiotis, C. A., & Lombard, D. B. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7264 · Cited by 140 · see citing works
MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4
Lang, A., Grether‐Beck, S., Singh, M., Kuck, F., Jakob, S., Kefalas, A., Altinoluk-Hambüchen, S., Graffmann, N., Schneider, M., Lindecke, A., et al. (2016) · Aging · doi:10.18632/aging.100905 · Cited by 138 · see citing works
The Roles of Mitochondrial SIRT4 in Cellular Metabolism
Min, Z., Gao, J., & Yu, Y. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00783 · Cited by 135 · see citing works
Identification of SIRT3 as an eraser of H4K16la
Fan, Z., Liu, Z., Zhang, N., Wei, W., Cheng, K., Sun, H., & Hao, Q. (2023) · iScience · doi:10.1016/j.isci.2023.107757 · Cited by 129 · see citing works
Cuproptosis and cuproptosis–related genes in rheumatoid arthritis: Implication, prospects, and perspectives
Zhao, J., Guo, S., Schrodi, S. J., & He, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.930278 · Cited by 124 · see citing works
The Current State of NAD+‐Dependent Histone Deacetylases (Sirtuins) as Novel Therapeutic Targets
Schiedel, M., Robaa, D., Rumpf, T., Sippl, W., & Jung, M. (2017) · Medicinal Research Reviews · doi:10.1002/med.21436 · Cited by 122 · see citing works
Potential Modulation of Sirtuins by Oxidative Stress
Santos, L., Escande, C., & Denicola, A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9831825 · Cited by 115 · see citing works
Protein lipoylation: mitochondria, cuproptosis, and beyond
Lin, C.-H., Chin, Y., Zhou, M., Sobol, R. W., Hung, M., & Tan, M. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.04.002 · Cited by 116 · see citing works
Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH
Madsen, A. S., Andersen, C. D., Daoud, M., Anderson, K. A., Laursen, J. S., Chakladar, S., Huynh, F. K., Colaço, A. R., Backos, D. S., Fristrup, P., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.668699 · Cited by 110 · see citing works
Sirtuins in vascular diseases: Emerging roles and therapeutic potential
D’Onofrio, N., Vitiello, M., Casale, R., Servillo, L., Giovane, A., & Balestrieri, M. L. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.001 · Cited by 104 · see citing works
Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features
Pannek, M., Simic, Z., Fuszard, M. A., Meleshin, M., Rotili, D., Mai, A., Schutkowski, M., & Steegborn, C. (2017) · Nature Communications · doi:10.1038/s41467-017-01701-2 · Cited by 102 · see citing works
Sirtuins' control of autophagy and mitophagy in cancer
Aventaggiato, M., Vernucci, E., Barreca, F., Russo, M. A., & Tafani, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107748 · Cited by 103 · see citing works
Chemical and structural biology of protein lysine deacetylases
Yoshida, M., Kudo, N., Kosono, S., & Ito, A. (2017) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.93.019 · Cited by 102 · see citing works
Rhizobacteria protective hydrogel to promote plant growth and adaption to acidic soil
Feng, Q., Luo, Y., Liang, M., Cao, Y., Wang, L. M., Liu, C., Zhang, X., Ren, L., Wang, Y., Wang, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56988-3 · Cited by 99 · see citing works
Targeting sirtuins for cancer therapy: epigenetics modifications and beyond
Shen, H., Qi, X., Hu, Y., Wang, Y., Zhang, J., Liu, Z., & Qin, Z. (2024) · Theranostics · doi:10.7150/thno.100667 · Cited by 95 · see citing works
Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome
Mauvoisin, D., Atger, F., Dayon, L., Galindo, A. N., Wang, J., Martín, E., Silva, L. D., Montoliu, I., Collino, S., Martin, F., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.065 · Cited by 91 · see citing works
Post-translational Modifications Regulate Class IIa Histone Deacetylase (HDAC) Function in Health and Disease
Mathias, R. A., Guise, A. J., & Cristea, I. M. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o114.046565 · Cited by 93 · see citing works
Self-citation
Sirtuin Inhibition: Strategies, Inhibitors, and Therapeutic Potential
Jiang, Y., Liu, J., Chen, D., Yan, L., & Zheng, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.01.009 · Cited by 93 · see citing works
Matrix Redox Physiology Governs the Regulation of Plant Mitochondrial Metabolism through Posttranslational Protein Modifications
Møller, I. M., Igamberdiev, A. U., Bykova, N. V., Finkemeier, I., Rasmusson, A. G., & Schwarzländer, M. (2020) · The Plant Cell · doi:10.1105/tpc.19.00535 · Cited by 89 · see citing works
Sirtuins in atherosclerosis: guardians of healthspan and therapeutic targets
Grootaert, M. O. J., & Bennett, M. R. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00685-x · Cited by 88 · see citing works
Mitochondrial Sirtuins in cardiometabolic diseases
Tang, X., Chen, X., Chen, H., & Liu, D. (2017) · Clinical Science · doi:10.1042/cs20160685 · Cited by 87 · see citing works
Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives
Luo, Z., Yao, J., Wang, Z., & Xu, J. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04286-1 · Cited by 87 · see citing works
Sirtuins in Alzheimer’s Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics
Cacabelos, R., Carril, J. C., Cacabelos, N., Kazantsev, A. G., Vostrov, A. A., Corzo, L., Cacabelos, P., & Goldgaber, D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051249 · Cited by 86 · see citing works
Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis
Tajima, K., Ikeda, K., Chang, H., Chang, C., Yoneshiro, T., Oguri, Y., Jun, H., Wu, J., Ishihama, Y., & Kajimura, S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0106-z · Cited by 86 · see citing works
Chiral Posttranslational Modification to Lysine ε-Amino Groups
Moreno-Yruela, C., Bæk, M., Monda, F., & Olsen, C. A. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.2c00115 · Cited by 85 · see citing works
Ovarian aging: energy metabolism of oocytes
Bao, S., Yin, T., & Liu, S. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01427-y · Cited by 85 · see citing works
Lysine acetylation in mitochondria: From inventory to function
Hosp, F., Lassowskat, I., Santoro, V., Vleesschauwer, D. D., Fliegner, D., Redestig, H., Mann, M., Christian, S., Hannah, M. A., & Finkemeier, I. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.07.012 · Cited by 85 · see citing works
Who watches the watchmen? Regulation of the expression and activity of sirtuins
Buler, M., Andersson, U., & Hakkola, J. (2016) · The FASEB Journal · doi:10.1096/fj.201600410rr · Cited by 84 · see citing works
Mesenchymal stromal cell-derived exosomes improve mitochondrial health in pulmonary arterial hypertension
Hogan, S. E., Rodriguez, M. P., Cheadle, J. B., Glenn, R. A., Medrano, C., Petersen, T. H., & Ilagan, R. M. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00058.2018 · Cited by 82 · see citing works
Sirtuins and the Metabolic Hurdles in Cancer
German, N. J., & Haigis, M. C. (2015) · Current Biology · doi:10.1016/j.cub.2015.05.012 · Cited by 84 · see citing works
Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster
Wood, J. G., Schwer, B., Wickremesinghe, P. C., Hartnett, D. A., Burhenn, L., Garcia, M., Li, M., Verdin, E. M., & Helfand, S. L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720673115 · Cited by 83 · see citing works
Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer
Tomaselli, D., Steegborn, C., Mai, A., & Rotili, D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00474 · Cited by 80 · see citing works
Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance
Bahl, S., & Seto, E. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03599-4 · Cited by 82 · see citing works
Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential
George, J., & Ahmad, N. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2733 · Cited by 81 · see citing works
Identification of GLS as a cuproptosis-related diagnosis gene in acute myocardial infarction
Liu, Z., Wang, L., Xing, Q., Liu, X., Hu, Y., Li, W., Yan, Q., Liu, R., & Huang, N. J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1016081 · Cited by 81 · see citing works
Mitochondrial Function, Metabolic Regulation, and Human Disease Viewed through the Prism of Sirtuin 4 (SIRT4) Functions
Betsinger, C. N., & Cristea, I. M. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00086 · Cited by 80 · see citing works
Self-citation
NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects
Dölle, C., Skoge, R. H., VanLinden, M. R., & Ziegler, M. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660206 · Cited by 78 · see citing works
Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis
Tao, J., Zhang, J., Ling, Y., McCall, C. E., & Liu, T. F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00419 · Cited by 77 · see citing works
A comprehensive review of Sirtuins: With a major focus on redox homeostasis and metabolism
Shahgaldi, S., & Kahmini, F. R. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119803 · Cited by 79 · see citing works
Sirtuin family in autoimmune diseases
Tao, Z., Jin, Z., Wu, J., Cai, G., & Yu, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1186231 · Cited by 79 · see citing works
Nicotinamide Adenine Dinucleotide Metabolism and Neurodegeneration
Pehar, M., Harlan, B. A., Killoy, K. M., & Vargas, M. R. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7145 · Cited by 77 · see citing works
The Aging Metabolome—Biomarkers to Hub Metabolites
Sharma, R. B., & Ramanathan, A. (2020) · PROTEOMICS · doi:10.1002/pmic.201800407 · Cited by 76 · see citing works
Mitochondrial Sirtuins in Reproduction
Emidio, G. D., Falone, S., Artini, P. G., Amicarelli, F., D’Alessandro, A. M., & Tatone, C. (2021) · Antioxidants · doi:10.3390/antiox10071047 · Cited by 74 · see citing works
Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism
Jeong, S. M., & Haigis, M. C. (2015) · Molecules and Cells · doi:10.14348/molcells.2015.0167 · Cited by 74 · see citing works
A global view of the human post-translational modification landscape
Kitamura, N., & Galligan, J. J. (2023) · Biochemical Journal · doi:10.1042/bcj20220251 · Cited by 70 · see citing works
SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones
Jin, J., He, B., Zhang, X., Lin, H., & Wang, Y. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b04977 · Cited by 73 · see citing works
SIRT 4 is essential for metabolic control and meiotic structure during mouse oocyte maturation
Zeng, J., Jiang, M., Wu, X., Diao, F., Qiu, D., Hou, X., Wang, H., Li, L., Li, C., Ge, J., et al. (2018) · Aging Cell · doi:10.1111/acel.12789 · Cited by 73 · see citing works
Using mitochondrial sirtuins as drug targets: disease implications and available compounds
Gertz, M., & Steegborn, C. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2180-7 · Cited by 71 · see citing works
Keeping the balance in NAD metabolism
Strømland, Ø., Niere, M., Nikiforov, A. A., VanLinden, M. R., Heiland, I., & Ziegler, M. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180417 · Cited by 72 · see citing works
Updates on the epigenetic roles of sirtuins
Kosciuk, T., Wang, M., Hong, J. Y., & Lin, H. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.01.023 · Cited by 70 · see citing works
Mitochondrial responsibility in ageing process: innocent, suspect or guilty
López‐Lluch, G., Santos‐Ocaña, C., Sánchez-Alcázar, J. A., Fernández‐Ayala, D. J. M., Asencio, C., Rodríguez‐Aguilera, J. C., & Navas, P. (2015) · Biogerontology · doi:10.1007/s10522-015-9585-9 · Cited by 69 · see citing works
Extranuclear Sirtuins and Metabolic Stress
Elkhwanky, M., & Hakkola, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7270 · Cited by 67 · see citing works
Therapeutic Potential and Activity Modulation of the Protein Lysine Deacylase Sirtuin 5
Fiorentino, F., Castiello, C., Mai, A., & Rotili, D. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00687 · Cited by 69 · see citing works
The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
Stacpoole, P. W., & McCall, C. E. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.02.007 · Cited by 68 · see citing works
The sirtuin family in cancer
Costa‐Machado, L. F., & Fernández-Marcos, P. J. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1634953 · Cited by 66 · see citing works
CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases
Lambrechts, R. A., Schepers, H., Yu, Y., van der Zwaag, M., Autio, K. J., Vieira‐Lara, M. A., Bakker, B. M., Tijssen, M. A. J., Hayflick, S. J., Grzeschik, N. A., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910488 · Cited by 67 · see citing works
SIRT4 is an early regulator of branched-chain amino acid catabolism that promotes adipogenesis
Zaganjor, E., Yoon, H., Spinelli, J. B., Nunn, E. R., Laurent, G., Keskinidis, P., Sivaloganathan, S., Joshi, S., Notarangelo, G., Mulei, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109345 · Cited by 67 · see citing works
The Role of SIRT3 in the Brain Under Physiological and Pathological Conditions
Sidorova‐Darmos, E., Sommer, R., & Eubanks, J. H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00196 · Cited by 66 · see citing works
SIRT4 and Its Roles in Energy and Redox Metabolism in Health, Disease and During Exercise
Han, Y., Zhou, S., Coetzee, S., & Chen, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01006 · Cited by 69 · see citing works
Targeting glutamine metabolism in hepatic stellate cells alleviates liver fibrosis
Yin, X.-C., Peng, J., Gu, L.-H., Liu, Y., Li, X., Wu, J.-H., Xu, B., Zhuge, Y., & Zhang, F. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05409-0 · Cited by 62 · see citing works
Distinctive Roles of Sirtuins on Diabetes, Protective or Detrimental?
Song, J., Yang, B., Jia, X., Li, M., Tan, W. F., Ma, S., Shi, X., & Feng, L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00724 · Cited by 66 · see citing works
Sirtuins in mitochondrial stress: Indispensable helpers behind the scenes
Lin, S., Xing, H., Zang, T., Ruan, X., Wo, L., & He, M. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.03.006 · Cited by 65 · see citing works

Identification of Sirtuin4 (SIRT4) Protein Interactions: Uncovering Candidate Acyl-Modified Mitochondrial Substrates and Enzymatic Regulators
Mathias, R. A., Greco, T. M., & Cristea, I. M. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3667-0_15 · Cited by 17 · see citing works
Self-citation
Emerging regulatory roles of mitochondrial sirtuins on pyruvate dehydrogenase complex and the related metabolic diseases: Review
Nasiri, A., Sadeghi, M., Vaisi‐Raygani, A., Kiani, S., Aghelan, Z., & Khodarahmi‬, R. (2020) · Biomedical Research and Therapy · doi:10.15419/bmrat.v7i2.591 · Cited by 10 · see citing works
The Roles of Mitochondrial SIRT4 in Cellular Metabolism
Min, Z., Gao, J., & Yu, Y. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00783 · Cited by 135 · see citing works
New roles for sirtuins in mitochondrial metabolism
Haigis, M. C. (2010) · The FASEB Journal · doi:10.1096/fasebj.24.1_supplement.198.2
Mitochondrial Function, Metabolic Regulation, and Human Disease Viewed through the Prism of Sirtuin 4 (SIRT4) Functions
Betsinger, C. N., & Cristea, I. M. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00086 · Cited by 80 · see citing works
Self-citation

Authors: Mathias, R. A., Greco, T. M., Oberstein, A., Budayeva, H. G., Chakrabarti, R., Rowland, E. A., Kang, Y., Shenk, T., & Cristea, I. M.
Affiliations: La Trobe University (AU)
Princeton University (US)
Corresponding author: Cristea, Ileana M.
ORCID: Mathias, Rommel A.
Greco, Todd M.
Budayeva, Hanna G.
Chakrabarti, Rumela
Kang, Yibin
Shenk, Thomas
Cristea, Ileana M.
Venue: Cell
Publisher: Elsevier BV
Published: 2014-12
Volume: 159
Issue: 7
Pages: 1615-1625
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.11.046
PMC: PMC4344121
OpenAlex: W2134920945
Cited by: 430
References: 51
Citations by year: 2026: 20 · 2025: 30 · 2024: 29 · 2023: 34 · 2022: 48 · 2021: 46 · 2020: 41 · 2019: 38 · 2018: 43 · 2017: 35 · 2016: 40 · 2015: 25 · 2013: 1
FWCI: 16.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (DP1DA026192)
National Cancer Institute (CA 82396, R01CA082396)
National Institute of Allergy and Infectious Diseases (AI78063, R33AI102187, R21AI102187, R01AI078063)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD073044)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: SIRT4, pyruvate dehydrogenase complex, mitochondrial sirtuins, acetyl-CoA biosynthesis, hepatic metabolism
MeSH terms: Amidohydrolases, Animals, Glutamine, Humans, Thioctic Acid, Liver, Mitochondria, Pyruvate Dehydrogenase Complex, Mitochondrial Proteins, Sirtuins, Mice, Rats, Gene Knockdown Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks