The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α
Open accessAbstract
SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
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
Cites
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?
Bioinformatic analysis identified SIRT6 as a third miR-33 predicted target involved in glucose homeostasis.
“In addition to IRS2 and FRS2, our bioinformatic analysis identified a third miR-33 predicted target involved in glucose homeostasis: the histone deacetylase SIRT6 (25, 26).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [26]
SIRT6-deficient mice develop normally but succumb to lethal hypoglycemia early in life, suggesting an important role of SIRT6 in regulating glucose metabolism.
“SIRT6-deficient mice develop normally but succumb to lethal hypoglycemia early in life, suggesting an important role of SIRT6 in regulating glucose metabolism (25, 26).”
From miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling (2011) · cites this paper as [26]
SirT6 represses HIF-1α-mediated transcription by binding to chromatin on HREs and attenuating activation of glycolytic genes via deacetylating histones around promoters.
“In addition, SirT6 has been shown to repress HIF-1α-mediated transcription by binding to chromatin on HREs and attenuating the activation of glycolytic genes via deacetylating histones around the promoters (Zhong et al., 2010).”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Zhong et al., 2010
SIRT6 activation coordinately regulates expression of glycolytic genes, and mice deficient in SIRT6 have severe metabolic defects, signs of accelerated aging, and die prematurely.
“SIRT6 activation coordinately regulates the expression of glycolytic genes (479), and mice deficient in SIRT6 have severe metabolic defects, signs of accelerated aging, and die prematurely.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [479]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · see citing works
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · see citing works
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · see citing works
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300 · see citing works
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Carmeliet, P., Dor, Y., Herbert, J.-M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., et al. (1998) · Nature · doi:10.1038/28867 · Cited by 2,502 · see citing works
Self-citationHIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267 · see citing works
TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019 · see citing works
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924 · see citing works
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · see citing works
Self-citationRecent progress in the biology and physiology of sirtuins
Finkel, T., Deng, C., & Mostoslavsky, R. (2009) · Nature · doi:10.1038/nature08197 · Cited by 1,484 · see citing works
Self-citationPhylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
Frye, R. A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3000 · Cited by 1,409 · see citing works
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295 · see citing works
HIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells
Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225 · see citing works
SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L. A., Barrett, J. C., et al. (2008) · Nature · doi:10.1038/nature06736 · Cited by 1,111 · see citing works
Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice
Cheng, H.-L., Mostoslavsky, R., Saito, S., Manis, J. P., Gu, Y., Patel, P., Bronson, R., Appella, E., Alt, F. W., & Chua, K. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934713100 · Cited by 1,095 · see citing works
Self-citationKawahara, T. L. A., Michishita, E., Adler, A. S., Damian, M., Berber, E., Lin, M., McCord, R. A., Ongaigui, K. C. L., Boxer, L. D., Chang, H. Y., et al. (2009) · Cell · doi:10.1016/j.cell.2008.10.052 · Cited by 1,090 · see citing works
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885 · see citing works
Lu, H., Forbes, R. A., & Verma, A. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202487200 · Cited by 839 · see citing works
An essential role for p300/CBP in the cellular response to hypoxia
Arany, Z., Huang, L. E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M. A., Bunn, H. F., & Livingston, D. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12969 · Cited by 790 · see citing works
Regulation and Destabilization of HIF-1α by ARD1-Mediated Acetylation
Jeong, J.-W., Bae, M.-K., Ahn, M.-Y., Kim, S.-H., Sohn, T.-K., Bae, M.-H., Yoo, M.-A., Song, E. J., Lee, K.-J., & Kim, K.-W. (2002) · Cell · doi:10.1016/s0092-8674(02)01085-1 · Cited by 716 · see citing works
Kallio, P., Okamoto, K., O'Brien, S., Carrero, P., Makino, Y., Tanaka, H., & Poellinger, L. (1998) · EMBO Journal · doi:10.1093/emboj/17.22.6573 · Cited by 707 · see citing works
Nutrient Availability Regulates SIRT1 Through a Forkhead-Dependent Pathway
Nemoto, S., Fergusson, M. M., & Finkel, T. (2004) · Science · doi:10.1126/science.1101731 · Cited by 671 · see citing works
Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells
Seagroves, T. N., Ryan, H. E., Lu, H., Wouters, B. G., Knapp, M., Thibault, P., Laderoute, K. R., & Johnson, R. S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3436-3444.2001 · Cited by 634 · see citing works
Sirtuins in aging and age-related disease
Longo, V. D., & Kennedy, B. K. (2006) · Cell · doi:10.1016/j.cell.2006.07.002 · Cited by 628 · see citing works
Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX
Bassing, C. H., Chua, K. F., Sekiguchi, J., Suh, H., Whitlow, S. R., Fleming, J. C., Monroe, B., Ciccone, D. N., Yan, C. T., Vlasáková, K., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122228699 · Cited by 525 · see citing works
Bmi1 regulates mitochondrial function and the DNA damage response pathway
Liu, J., Cao, L., Chen, J., Song, S., Lee, I. H., Quijano, C., Liu, H., Keyvanfar, K., Chen, H., Cao, L.-Y., et al. (2009) · Nature · doi:10.1038/nature08040 · Cited by 474 · see citing works
Lum, J. J., Bui, T., Gruber, M., Gordan, J. D., DeBerardinis, R. J., Covello, K. L., Simon, M. C., & Thompson, C. B. (2007) · Genes & Development · doi:10.1101/gad.1529107 · Cited by 429 · see citing works
Mammalian Facilitative Glucose Transporter Family: Structure and Molecular Regulation
Pessin, J. E., & Bell, G. I. (1992) · Annual Review of Physiology · doi:10.1146/annurev.ph.54.030192.004403 · Cited by 422 · see citing works
Xia, X., Lemieux, M. E., Li, W., Carroll, J. S., Brown, M., Liu, X. S., & Kung, A. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810067106 · Cited by 410 · see citing works
Transcription Regulation Through Promoter-Proximal Pausing of RNA Polymerase II
Core, L. J., & Lis, J. T. (2008) · Science · doi:10.1126/science.1150843 · Cited by 406 · see citing works
Oxygen Sensors at the Crossroad of Metabolism
Aragonés, J., Fraisl, P., Baes, M. I., & Carmeliet, P. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.10.001 · Cited by 290 · see citing works
Lewis, G. D., Wei, R., Liu, E. H., Yang, E., Shi, X., Martinovic, M. F., Farrell, L. A., Asnani, A. H., Cyrille, M., Ramanathan, A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35111 · Cited by 283 · see citing works
Hu, C., Iyer, S. R., Sataur, A., Covello, K. L., Chodosh, L. A., & Simon, M. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3514-3526.2006 · Cited by 267 · see citing works
CDK8 Is a Stimulus-Specific Positive Coregulator of p53 Target Genes
Donner, A. J., Szostek, S. A., Hoover, J. M., & Espinosa, J. M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.026 · Cited by 253 · see citing works
Self-citationHIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans
Chen, D., Thomas, E. L., & Kapahi, P. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000486 · Cited by 250 · see citing works
Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans
Mehta, R., Steinkraus, K. A., Sutphin, G. L., Ramos, F. J., Shamieh, L. S., Huh, A., Davis, C., Chandler-Brown, D. B., & Kaeberlein, M. R. (2009) · Science · doi:10.1126/science.1173507 · Cited by 243 · see citing works
Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases
Hirota, K., & Semenza, G. L. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.193 · Cited by 231 · see citing works
The Role of Sirtuins in the Control of Metabolic Homeostasis
Yu, J., & Auwerx, J. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04952.x · Cited by 196 · see citing works
Zimmer, M., Ebert, B. L., Neil, C., Brenner, K., Papaioannou, I., Melas, A., Tolliday, N., Lamb, J., Pantopoulos, K., Golub, T., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.12.004 · Cited by 191 · see citing works
Self-citationRole of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance
Kilic, M., Kasperczyk, H., Fulda, S., & Debatin, K. (2006) · Oncogene · doi:10.1038/sj.onc.1210008 · Cited by 167 · see citing works
Imaging of mediastinal lymph nodes: CT, MR, and FDG PET.
Boiselle, P. M., Patz, E. F., Vining, D. J., Weissleder, R., Shepard, J. A., & McLoud, T. C. (1998) · Radiographics · doi:10.1148/radiographics.18.5.9747607 · Cited by 129 · see citing works
Self-citationAssessing IRES activity in the HIF-1α and other cellular 5′ UTRs
Bert, A. G., Grépin, R., Vadas, M. A., & Goodall, G. J. (2006) · RNA · doi:10.1261/rna.2320506 · Cited by 121 · see citing works
Interaction between HIF‐1α (ODD) and hARD1 does not induce acetylation and destabilization of HIF‐1α
Arnesen, T., Kong, X., Evjenth, R., Gromyko, D., Varhaug, J. E., Zhao, L., Sang, N., Caro, J., & Lillehaug, J. R. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.10.036 · Cited by 87 · see citing works
Barzilai, N., & Bartke, A. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/gln061 · Cited by 69 · see citing works
Serikawa, K. A., Xu, X. L., MacKay, V. L., Law, G. L., Zong, Q., Zhao, L. P., Bumgarner, R. E., & Morris, D. R. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.d200002-mcp200 · Cited by 53 · see citing works
Xu, J., Chang, V. C., Joseph, S. B., Trujillo, C., Bassilian, S., Saad, M. F., Lee, W. N. P., & Kurland, I. J. (2003) · Endocrinology · doi:10.1210/en.2003-1173 · Cited by 50 · see citing works
Self-citationPurified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF‐1α fragments in vitro
Murray-Rust, T. A., Oldham, N. J., Hewitson, K. S., & Schofield, C. J. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.02.012 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693 · see citing works
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
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function
Sukumar, M., Liu, J., Ji, Y., Subramanian, M., Crompton, J. G., Yu, Z., Roychoudhuri, R., Palmer, D. C., Muranski, P., Karoly, E. D., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69589 · Cited by 952 · see citing works
Sirtuin 1 Modulates Cellular Responses to Hypoxia by Deacetylating Hypoxia-Inducible Factor 1α
Lim, J.-H., Lee, Y.-M., Chun, Y.-S., Chen, J., Kim, J.-E., & Park, J.-W. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.023 · Cited by 758 · 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
Self-citationmiR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670 · see citing works
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
Sebastián, C., Zwaans, B. M. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.047 · Cited by 660 · see citing works
Self-citationFeldman, J. L., Baeza, J., & Denu, J. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.511261 · Cited by 637 · see citing works
“However, several prior studies indicated that SIRT6 acted through deacetylation of histonemarksH3K9Ac (14) and H3K56Ac (15), which modulated HIF1- -dependent (16), NF- B-dependent (17), and c-Myc-dependent (3) pathways.”
BackgroundMechanisms and Implications of Metabolic Heterogeneity in Cancer
Kim, J., & DeBerardinis, R. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.013 · Cited by 606 · see citing works
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
The updated biology of hypoxia-inducible factor
Greer, S. N., Metcalf, J. L., Wang, Y., & Ohh, M. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.125 · Cited by 545 · see citing works
Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)
Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534 · see citing works
LINE1 Derepression in aged wild-type and SIRT6-deficient mice drives inflammation
Simon, M., Van Meter, M., Ablaeva, J., Ke, Z., Gonzalez, R. S., Taguchi, T., De Cecco, M., Leonova, K. I., Kogan, V., Helfand, S. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.014 · Cited by 498 · see citing works
Sirtuins, a promising target in slowing down the ageing process
Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017) · Biogerontology · doi:10.1007/s10522-017-9685-9 · Cited by 470 · see citing works
Calorie restriction and sirtuins revisited
Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · see citing works
Splicing-directed therapy in a new mouse model of human accelerated aging
Osorio, F. G., Navarro, C. L., Cadiñanos, J., López-Mejía, I. C., Quirós, P. M., Bartoli, C., Rivera, J., Tazi, J., Guzmán, G., Varela, I., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002847 · Cited by 432 · see citing works
Bell, E. L., Emerling, B. M., Ricoult, S. J. H., & Guarente, L. (2011) · Oncogene · doi:10.1038/onc.2011.37 · Cited by 440 · see citing works
SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling
Toiber, D., Erdel, F., Bouazoune, K., Silberman, D. M., Zhong, L., Mulligan, P., Sebastian, C., Cosentino, C., Martinez-Pastor, B., Giacosa, S., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.018 · Cited by 381 · see citing works
Self-citationNuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · 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
Wang, D. D., Toledo, E., Hruby, A., Rosner, B. A., Willett, W. C., Sun, Q., Razquin, C., Zheng, Y., Ruiz-Canela, M., Guasch-Ferré, M., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024261 · Cited by 327 · see citing works
Self-citationMetabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322 · see citing works
Connecting threads: epigenetics and metabolism
Katada, S., Imhof, A., & Sassone-Corsi, P. (2012) · Cell · doi:10.1016/j.cell.2012.01.001 · Cited by 315 · see citing works
Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism
Masri, S., Rigor, P., Cervantes, M., Ceglia, N., Sebastian, C., Xiao, C., Roqueta-Rivera, M., Deng, C., Osborne, T. F., Mostoslavsky, R., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.050 · Cited by 292 · see citing works
Self-citationCrosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes
Cantó, C., Sauve, A. A., & Bai, P. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.004 · Cited by 246 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · 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
NAD <sup>+</sup> metabolism: A therapeutic target for age-related metabolic disease
Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.789479 · Cited by 193 · see citing works
“Additionally, Sirt6 / mice have reduced insulinlike growth factor 1 levels and are severely hypoglycemic (Mostoslavsky et al., 2006), possibly mediated by the hypoxia-inducible factors-1a-dependent activation of glycolysis and subsequent decreases in glucose levels (Zhong et al., 2010).”
BackgroundSkeletal Muscle Hypoxia-inducible Factor-1 and Exercise
Lindholm, M. E., & Rundqvist, H. (2016) · Experimental Physiology · doi:10.1113/ep085318 · Cited by 156 · see citing works
Sirtuin‐dependent epigenetic regulation in the maintenance of genome integrity
Bosch‐Presegué, L., & Vaquero, A. (2015) · The FEBS Journal · doi:10.1111/febs.13053 · Cited by 132 · see citing works
Mouse Models to Disentangle the Hallmarks of Human Aging
Folgueras, A. R., Freitas-Rodríguez, S., Velasco, G., & López-Otín, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312204 · Cited by 113 · see citing works
Policastro, L. L., Ibañez, I. L., Notcovich, C., Duran, H. A., & Podhajcer, O. L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4367 · Cited by 120 · see citing works
Circadian Rhythms and Mitochondria: Connecting the Dots
Sardon Puig, L., Valera-Alberni, M., Cantó, C., & Pillon, N. J. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00452 · Cited by 113 · see citing works
Identification of and molecular basis for sirt6 loss-of-function point mutations in cancer
Kugel, S., Feldman, J. L., Klein, M. A., Silberman, D. M., Sebastián, C., Mermel, C., Dobersch, S., Clark, A. R., Getz, G., Denu, J. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.022 · Cited by 81 · see citing works
Matsuura, H., Ichiki, T., Inoue, E., Nomura, M., Miyazaki, R., Hashimoto, T., Ikeda, J., Takayanagi, R., Fong, G.-H., & Sunagawa, K. (2013) · Circulation · doi:10.1161/circulationaha.113.001742 · Cited by 77 · see citing works
Bao, J., & Sack, M. N. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0402-y · Cited by 67 · see citing works
Andrysik, Z., Bender, H., Galbraith, M. D., & Espinosa, J. M. (2021) · Nature Communications · doi:10.1038/s41467-021-21687-2 · Cited by 63 · see citing works
Self-citationA continuous, fluorogenic sirtuin 2 deacylase assay: substrate screening and inhibitor evaluation
Galleano, I., Schiedel, M., Jung, M., Madsen, A. S., & Olsen, C. A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01532 · Cited by 53 · see citing works
Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition
Li, C., Fu, C., Zhou, W., Li, H., Liu, Z., Wu, G., He, T., Shen, M., & Liu, H. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02366-x · Cited by 45 · see citing works
“HIF-1α is known to interact with both activators and repressors of transcription, such as BRG1, SIRT6, and EZH2 [39, 40], depending on the chromatin context.”
Metabolic Dysfunction in Hutchinson–Gilford Progeria Syndrome
Kreienkamp, R., & Gonzalo, S. (2020) · Cells · doi:10.3390/cells9020395 · Cited by 45 · see citing works
Minic, Z., Li, Y., Hüttmann, N., Uppal, G. K., D’Mello, R., & Berezovski, M. V. (2023) · Biomedicines · doi:10.3390/biomedicines11041076 · Cited by 20 · see citing works
MacDonald, I. M., Moen, C., Duncan, J. L., Tsang, S. H., Cehajic-Kapetanovic, J., & Aleman, T. S. (2020) · Translational Vision Science & Technology · doi:10.1167/tvst.9.3.17 · Cited by 20 · see citing works
Maldonado, M., Chen, J., Duan, H., Huang, T., Jiang, G., & Zhong, Y. (2021) · Translational Medicine of Aging · doi:10.1016/j.tma.2021.02.001 · Cited by 11 · see citing works
- Authors
- Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., Guimaraes, A., Marinelli, B., Wikstrom, J. D., Nir, T., Clish, C. B., Vaitheesvaran, B., Iliopoulos, O., Kurland, I., Dor, Y., Weissleder, R., Shirihai, O. S., Ellisen, L. W., Espinosa, J. M., & Mostoslavsky, R.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Massachusetts General Hospital (US)
- Hebrew University of Jerusalem (IL)
- Broad Institute (US)
- Albert Einstein College of Medicine (US)
- Boston University (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 140
- Issue
- 2
- Pages
- 280-293
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2821045
- OpenAlex
- W2109560454
- Cited by
- 1,001
- References
- 50
- Citations by year
- 2026: 34 · 2025: 39 · 2024: 36 · 2023: 51 · 2022: 60 · 2021: 84 · 2020: 68 · 2019: 59 · 2018: 68 · 2017: 67 · 2016: 87 · 2015: 76 · 2014: 62 · 2013: 83 · 2012: 55
- FWCI
- 26.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA117907, R01CA122589)
- National Institute of General Medical Sciences (R01GM093072)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK035914, R01DK088190, R01DK056690, R01DK058132)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- SIRT6, histone deacetylase, HIF-1α, glucose homeostasis, glycolysis, hypoglycemia, glucose uptake, mitochondrial respiration, chromatin regulation, corepressors, diabetes mellitus, obesity
- MeSH terms
- Animals, Glucose, Glycolysis, Mice, Knockout, Cell Respiration, Sirtuins, Glucose Transporter Type 1, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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
