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SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Open accessAbstract
Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins. Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting.
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In the citing paper
“Sirt3 is an established deacetylase whose targets include long chain acyl CoA dehydrogenase (LCAD), succinate dehydrogenase and Mn superoxide dismutase (SOD2) (Hirschey et al., 2010; Qiu et al., 2010).”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Hirschey et al., 2010
In the citing paper
“Additionally, higher NAD+ levels can promote the deacetylase and deacylase activity of both nuclear SIRT1 and mitochondrial SIRT3, which regulate mitochondrial function and protect from high-fat diet-induced metabolic disease42,81,85–88.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [85]
In the citing paper
“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“SIRT3 is upregulated during fasting (Hirschey et al. 2010) and more generally by PGC-1α (Kong et al. 2010), which allows it to best control the hyperacetylation caused by acetyl-CoA-dependent metabolic processes such as fatty acid oxidation and ketone body metabolism.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“These mice also share other characteristics of human disorders of fatty acid oxidation, including cold intolerance and reduced basal ATP levels ((Hirschey et al. 2010)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“SIRT3 promotes the efficient utilization of lipids as a primary source of acetyl-CoA during fasting by activating long-chain acyl-CoA dehydrogenase, a key enzyme in the β-oxidation of fatty acids, via deacetylation at K42 ((Hirschey et al. 2010)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“Mice lacking SIRT3 accumulate β-oxidation precursors and intermediates, including triglycerides and long-chain fatty acids.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Hirschey et al. 2010
In the citing paper
“In mice, SIRT3 is normally upregulated during fasting in liver and brown fat where it plays a role in fatty-acid oxidation by maintaining the deacetylation of long-chain acyl coenzyme A dehydrogenase in mitochondria (175).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [175]
In the citing paper
“In its absence, SIRT3-deficient mice show reduced utilization of lipid stores during fasting: they have decreased fatty acid oxidation, accumulate triglycerides, and have diminished production of hepatic ATP.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [175]
In the citing paper
“Upon fasting, SIRT3 expression is rapidly induced and deacetylates key residues on mitochondrial proteins (Hirschey et al, 2010).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Hirschey et al, 2010
In the citing paper
“One week of HFD enhanced SIRT3 levels and prevented mitochondrial hyperacetylation despite the higher levels of lipid substrates (Hirschey et al, 2010).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Hirschey et al, 2010
In the citing paper
“Dietary excess of lipids also dramatically changes mitochondrial protein acetylation.”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Hirschey et al, 2010
In the citing paper
“Conversely, prolonged HFD dramatically decreases SIRT3 expression, correlating with the appearance of mitochondrial hyperacetylation and mitochondrial dysfunction (Hirschey et al, 2010).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Hirschey et al, 2010
In the citing paper
“For instance, acetylation of long-chain fatty acyl-CoA dehydrogenase, one of the four enzymes involved in the mitochondrial fat oxidation pathway, causes its inactivation, leading to fat accumulation [154], [155].”
In the citing paper
“SIRT3 has been reported to regulate mitochondrial fatty acid β-oxidation via deacetylation of long-chain acyl-CoA dehydrogenase, which, when dysregulated, results in defective fatty acid oxidation (Hirschey et al., 2010).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Hirschey et al., 2010
In the citing paper
“which represents a key regulator of mitochondrial energy metabolism (Palacios et al., 2009; Hirschey et al., 2010, 2011; Anderson and Hirschey, 2012).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Hirschey et al., 2010
In the citing paper
“Interestingly, SIRT3 is present in mitochondria, where it regulates the acetylation and activity of a variety of metabolic enzymes, suggesting additional ways that it might affect mitochondrial ROS production 73.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [73]
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Citations
Cites
1 retracted
Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism
Taniguchi, C. M., Ueki, K., & Kahn, C. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23187 · Cited by 286
Self-citationRetractedA SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol
Morrison, W. R., & Smith, L. M. (1964) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40190-7 · Cited by 6,005
A Flexible System of Enzymatic Analysis
Lowry, O. H., & Passonneau, J. V. (1972) · Elsevier eBooks · doi:10.1016/b978-0-12-457950-7.x5001-3 · Cited by 4,050
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317
Self-citationSrere, P. A. (1969) · Methods in Enzymology · doi:10.1016/0076-6879(69)13005-0 · Cited by 2,005
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487
Regulation of hepatic fatty acid oxidation and ketone body production
McGarry, J. D., & Foster, D. W. (1980) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.49.070180.002143 · Cited by 1,460
A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291
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Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration
Kincaid, B., & Bossy‐Wetzel, E. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00048 · Cited by 317
Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective
Pérez, S., & Rius-Pérez, S. (2022) · Antioxidants · doi:10.3390/antiox11071394 · Cited by 312
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 312
SIRT3 regulation of mitochondrial oxidative stress
Bause, A. S., & Haigis, M. C. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.007 · Cited by 311
Dysregulated metabolism contributes to oncogenesis
Hirschey, M. D., DeBerardinis, R. J., Diehl, A. M., Drew, J. E., Frezza, C., Green, M. F., Jones, L. W., Ko, Y. H., Le, A., Lea, M. A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.10.002 · Cited by 316
Self-citationAnsari, A., Rahman, M. S., Saha, S. K., Saikot, F. K., Deep, A., & Kim, K. (2016) · Aging Cell · doi:10.1111/acel.12538 · Cited by 315
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305
Role of mitochondrial dysfunction in cancer progression
Hsu, C., Tseng, L., & Lee, H. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216641787 · Cited by 320
Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism
Walsh, C. T., Tu, B. P., & Tang, Y. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00510 · Cited by 315
Interplay between oxidant species and energy metabolism
Quijano, C., Trujillo, M., Castro, L., & Trostchansky, A. (2015) · Redox Biology · doi:10.1016/j.redox.2015.11.010 · Cited by 309
Nakagawa, T., & Guarente, L. (2011) · Journal of Cell Science · doi:10.1242/jcs.081067 · Cited by 292
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Kitada, M., Ogura, Y., Monno, I., & Koya, D. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00187 · Cited by 298
A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol
Gertz, M., Nguyen, G. T. T., Fischer, F. F., Suenkel, B., Schlicker, C., Fränzel, B., Tomaschewski, J., Aladini, F., Becker, C., Wolters, D. A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049761 · Cited by 286
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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
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Marcheva, B., Ramsey, K. M., Peek, C. B., Affinati, A., Maury, E., & Bass, J. (2013) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-25950-0_6 · Cited by 282
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Rafalski, V. A., & Brunet, A. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.007 · Cited by 294
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278
Braidy, N., Berg, J., Clement, J., Khorshidi, F., Poljak, A., Jayasena, T., Grant, R., & Sachdev, P. S. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7269 · Cited by 294
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Merksamer, P. I., Liu, Y., He, W., Hirschey, M. D., Chen, D., & Verdin, E. (2013) · Aging · doi:10.18632/aging.100544 · Cited by 275
Self-citationBeier, U. H., Angelin, A., Akimova, T., Wang, L., Liu, Y., Xiao, H., Koike, M. A., Hancock, S. A., Bhatti, T. R., Han, R., et al. (2015) · The FASEB Journal · doi:10.1096/fj.14-268409 · Cited by 282
Mitochondria as a Drug Target in Ischemic Heart Disease and Cardiomyopathy
Walters, A. M., Porter, G. A., & Brookes, P. S. (2012) · Circulation Research · doi:10.1161/circresaha.112.265660 · Cited by 272
Quirós, P. M., Ramsay, A. J., Sala, D., Fernández‐Vizarra, E., Rodríguez, F., Peinado, J. R., Fernández‐García, M. S., Vega, J. A., Enríquez, J. A., Zorzano, A., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.70 · Cited by 269
Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance
Xie, B., Wang, S., Jiang, N., & Li, J. J. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.11.019 · Cited by 268
Mitochondrial sirtuins: regulators of protein acylation and metabolism
He, W., Newman, J. C., Wang, M. Z., Ho, L., & Verdin, E. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.07.004 · Cited by 262
Self-citationJin, L., Geng, L., Ying, L., Shu, L., Ye, K., Yang, R., Liu, Y., Wang, Y., Cai, Y., Jiang, X. X., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.059631 · Cited by 268
Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders
Jęśko, H. M., Wencel, P. L., Strosznajder, R. P., & Strosznajder, J. B. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2110-y · Cited by 264
A 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
Self-citationSIRT3‐dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth
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Self-citationPirinen, E., Cantó, C., Jo, Y. S., Morato, L., Zhang, H., Menzies, K. J., Williams, E. G., Mouchiroud, L., Moullan, N., Hagberg, C., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.002 · Cited by 254
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Giralt, A., & Villarroya, F. (2012) · Biochemical Journal · doi:10.1042/bj20120030 · Cited by 258
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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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Feldman, J. L., Dittenhafer-Reed, K. E., & Denu, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.378877 · Cited by 248
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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 250
Li, F., He, X., Ye, D., Lin, Y., Yu, H., Yao, C., Huang, L., Zhang, J., Wang, F., Xu, S., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.017 · Cited by 244
Wang, Z., Sun, R., Wang, G., Chen, Z., Li, Y., Zhao, Y., Liu, D., Zhao, H., Zhang, F., Yao, J., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101343 · Cited by 243
Self-citationDual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3
Brenmoehl, J., & Hoeflich, A. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.04.002 · Cited by 248
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Xiong, Y., & Guan, K. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201202056 · Cited by 243
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Roth, M., & Chen, W. (2013) · Oncogene · doi:10.1038/onc.2013.120 · Cited by 242
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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
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Chen, T., Wang, H., Chang, C.-J., & Lee, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021314 · Cited by 250
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Sack, M. N., & Finkel, T. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a013102 · Cited by 242
The sirtuin family’s role in aging and age-associated pathologies
Hall, J. A., Dominy, J. E., Lee, Y., & Puigserver, P. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64094 · Cited by 240
Martínez‐Sánchez, N., Seoane‐Collazo, P., Contreras, C., Varela, L., Villarroya, J., Rial‐Pensado, E., Buqué, X., Aurrekoetxea, I., Delgado, T. C., Vázquez‐Martínez, R., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.014 · Cited by 238
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Softic, S., Meyer, J. G., Wang, G.-X., Gupta, M. K., Batista, T. M., Lauritzen, H. P. M. M., Fujisaka, S., Serra, D., Herrero, L., Willoughby, J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.003 · Cited by 227
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Yang, H., Zhou, L., Shi, Q., Zhao, Y., Lin, H., Zhang, M., Zhao, S., Yang, Y. A., Ling, Z., Guan, K., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591041 · Cited by 225
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Wang, X. X., Wang, D., Luo, Y., Myakala, K., Dobrinskikh, E., Rosenberg, A. Z., Levi, J., Kopp, J. B., Field, A. P., Hill, A., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017020222 · Cited by 232
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Alrob, O. A., Sankaralingam, S., Ma, C., Wagg, C. S., Fillmore, N., Jaswal, J. S., Sack, M. N., Lehner, R. S., Gupta, M. P., Michelakis, E. D., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu156 · Cited by 223
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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
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White, M. F., & Kahn, C. R. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101304 · Cited by 221
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Lee, J., Kim, Y., Liu, T., Hwang, Y. J., Hyeon, S. J., Im, H., Lee, K., Alvarez, V. E., McKee, A. C., Um, S., et al. (2018) · Aging Cell · doi:10.1111/acel.12679 · Cited by 213
SIRT3 deficiency exacerbates ischemia-reperfusion injury: implication for aged hearts
Porter, G. A., Urciuoli, W. R., Brookes, P. S., & Nadtochiy, S. M. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00027.2014 · Cited by 221
Lee, D., & Goldberg, A. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.489716 · Cited by 211
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Horton, J. L., Martin, O. J., Lai, L., Riley, N. M., Richards, A., Vega, R. B., Leone, T. C., Pagliarini, D. J., Muoio, D. M., Bedi, K. C., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.84897 · Cited by 212
Giralt, A., Hondares, E., Villena, J. A., Ribas, F., Díaz-Delfín, J., Giralt, M., Iglesias, R., & Villarroya, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202390 · Cited by 210
Zhou, X., Chen, M., Zeng, X., Yang, J., Deng, H., Yi, L., & Mt, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.530 · Cited by 208
Newman, J. C., He, W., & Verdin, E. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.404863 · Cited by 210
Self-citationYu, L., Gong, B., Duan, W., Fan, C., Zhang, J., Li, Z., Xue, X., Xu, Y., Meng, D., Li, B., et al. (2017) · Scientific Reports · doi:10.1038/srep41337 · Cited by 210
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
Sirtuins, Aging, and MetabolismPreprint
Guarente, L. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010629 · Cited by 213
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Hallows, W. C., Yu, W., & Denu, J. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.317404 · Cited by 201
Miller, V. J., Villamena, F. A., & Volek, J. S. (2018) · Journal of Nutrition and Metabolism · doi:10.1155/2018/5157645 · Cited by 205
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Overmyer, K. A., Evans, C. R., Qi, N., Minogue, C. E., Carson, J. J., Chermside‐Scabbo, C. J., Koch, L. G., Britton, S. L., Pagliarini, D. J., Coon, J. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.007 · Cited by 202
Tao, R., Vassilopoulos, A., Parisiadou, L., Yan, Y., & Gius, D. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5482 · Cited by 194
NAD+/NADH and skeletal muscle mitochondrial adaptations to exercise
White, A. T., & Schenk, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00054.2012 · Cited by 199
Pillai, V. B., Kanwal, A., Fang, Y. H., Sharp, W. W., Samant, S. A., Arbiser, J. L., & Gupta, M. P. (2017) · Oncotarget · doi:10.18632/oncotarget.16133 · Cited by 194
NAD + 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
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Zhang, C., McFarlane, C., Lokireddy, S., Masuda, S., Ge, X., Gluckman, P. D., Sharma, M., & Kambadur, R. (2012) · Diabetologia · doi:10.1007/s00125-011-2304-4 · Cited by 192
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Li, X., & Kazgan, N. (2011) · International Journal of Biological Sciences · doi:10.7150/ijbs.7.575 · Cited by 196
The human sirtuin family: Evolutionary divergences and functions
Vassilopoulos, A., Fritz, K. S., Petersen, D. R., & Gius, D. R. (2011) · Human Genomics · doi:10.1186/1479-7364-5-5-485 · Cited by 196
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Hsu, Y., Wu, Y., Yu, T.-H., & Wei, Y. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.011 · Cited by 189
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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 196
Zhang, X., Ji, R., Liao, X., Castillero, E., Kennel, P. J., Brunjes, D. L., Franz, M., Möbius‐Winkler, S., Drosatos, K., George, I., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.030486 · Cited by 187
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Sosnowska, B., Mazidi, M., Penson, P. E., Gluba-Brzózka, A., Rysz, J., & Banach, M. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.08.027 · Cited by 188
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Zhang, T., Liu, J., Shen, S., Tong, Q., Ma, X., & Lin, L. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0356-z · Cited by 188
Lee, J., Cevallos, S. A., Byndloss, M. X., Tiffany, C. R., Olsan, E. E., Butler, B. P., Young, B. M., Rogers, A. W. L., Nguyen, H., Kim, K., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.001 · Cited by 189
Metadata
- Authors
- Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., Stevens, R. D., Li, Y., Saha, A. K., Ruderman, N. B., Bain, J. R., Newgard, C. B., Farese Jr, R. V., Alt, F. W., Kahn, C. R., & Verdin, E.
- Affiliations
- Gladstone Institutes (US)
- University of Pittsburgh (US)
- Joslin Diabetes Center (US)
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Duke University (US)
- Cell Signaling Technology (United States) (US)
- Boston University (US)
- Corresponding author
- Verdin, Eric
- ORCID
- Venue
- Nature
- Published
- 2010-03
- Volume
- 464
- Issue
- 7285
- Pages
- 121-125
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2841477
- OpenAlex
- W2052751736
- Cited by
- 1,687
- References
- 44
- Citations by year
- 2026: 77 · 2025: 86 · 2024: 108 · 2023: 95 · 2022: 125 · 2021: 107 · 2020: 110 · 2019: 112 · 2018: 110 · 2017: 102 · 2016: 127 · 2015: 113 · 2014: 95 · 2013: 110 · 2012: 97
- FWCI
- 40.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r01dk019514-35)
- National Institute on Aging (K08AG022325)
- National Heart, Lung, and Blood Institute (P01HL068758)
- National Institute of Diabetes and Digestive and Kidney Diseases (L40 DK065607, R01DK067509, DK59637, U24DK059637, K01DK076573, P30DK026743, R01-DK-019514)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- SIRT3, sirtuins, mitochondrial fatty acid oxidation, protein deacetylation, long-chain acyl-CoA dehydrogenase, acetylation, fasting, liver, brown adipose tissue, cold sensitivity, ATP levels, triglycerides, NAD+-dependent deacetylase, metabolic stress, caloric restriction
- MeSH terms
- Acetylation, Adenosine Triphosphate, Animals, Body Temperature Regulation, Adipose Tissue, Brown, Carnitine, Cell Line, Cold Temperature, Fasting, Fatty Acids, Humans, Hypoglycemia, Liver, Male, Mitochondria, Oxidation-Reduction, Mass Spectrometry, Triglycerides, Up-Regulation, Caloric Restriction, Acyl-CoA Dehydrogenase, Long-Chain, Mice, Sirtuin 3
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