PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation
Open accessAbstract
SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer.
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PARP1 is the main PARP enzyme in mammalian tissues and consumes NAD+ during catalysis.
“PARP1 is the main PARP enzyme in mammalian tissues and utilize NAD+ during its catalysis”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Bai et al., 2011
Inhibiting PARP1 can raise cellular NAD+ by reducing its degradation.
“several studies have proposed that PARP1 inhibition can be used to promote increases in cellular levels of NAD+ by decreasing its degradation”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Bai et al., 2011
Mice lacking Parp1 have higher NAD+ levels, greater SIRT1 activity, and more mitochondrial biogenesis.
“Indeed, deletion of the Parp1 gene in mice increases NAD+ levels, SIRT1 activity and mitochondrial biogenesis83.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [83]
Muscle mitochondrial oxidative capacity is higher in Parp-1−/− mice, which protects them from insulin resistance caused by high-fat diet.
“As a consequence, mitochondrial oxidative capacity is enhanced in muscle of Parp-1−/− mice, protecting them against high-fat diet (HFD)-induced insulin resistance.”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
Deleting the Parp-1 gene in mice boosts oxidative metabolism and guards against obesity caused by diet.
“We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity.”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
Removing Parp-1 increases NAD+ availability and SIRT1 activity in skeletal muscle and brown adipose tissue.
“Genetic ablation of Parp-1 increases NAD+ availability and SIRT1 activity in tissues, such as skeletal muscle and brown adipose tissue (Bai et al., 2011).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
The success of Paribs is thought to depend on cancer cells' high reliance on PARP enzymes for DNA repair, but may also involve reprogramming cells toward oxidative metabolism.
“The success of Paribs is thought to rely on the high dependency of these cancer cells on PARP enzymes for DNA repair (Curtin and Szabo, 2013), but could also involve their capacity to reprogram cells towards oxidative metabolism (Bai et al., 2011).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
During this study's time frame, no toxicity or genomic instability appeared in MRL-45696-treated mice.
“Within the time-frame of this study, and in line with findings in Parp-1−/− mice (Bai et al., 2011) and in patients treated with Olaparib (Audeh et al., 2010; Bundred et al., 2013; Tutt et al., 2010), no toxicity or genomic instability was seen in MRL-45696-treated mice.”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
PARP activity falls in muscle during fasting, when lipid oxidation is favored.
“Oppositely, PARP activity was decreased in muscle upon fasting (Bai et al., 2011), when lipid oxidation is favored.”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
Earlier results indicated PARP activity rises with high-fat diet, likely favoring fat storage over burning.
“Indeed, previous results indicated that PARP activity is increased upon HFD (Bai et al., 2011), likely favouring fat storage over burning (Erener et al., 2012).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai et al., 2011
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Cites
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
Self-citationSmall molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796 · see citing works
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · 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
Self-citationNutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works
Self-citationSmall 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
The Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase
North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M., & Verdin, E. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00038-8 · Cited by 1,542 · see citing works
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 · see citing works
(ADP-ribose)n participates in DNA excision repair
Durkacz, B. W., Omidiji, O., Gray, D. A., & Shall, S. (1980) · Nature · doi:10.1038/283593a0 · Cited by 1,123 · see citing works
Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells
Murcia, J. M., Niedergang, C., Trucco, C., Ricoul, M., Dutrillaux, B., Mark, M. P., Oliver, F. J., Masson, M., Dierich, A., LeMeur, M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7303 · Cited by 1,058 · see citing works
Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002 · see citing works
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J., Lamming, D. W., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.035 · Cited by 950 · see citing works
Self-citationCantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · see citing works
Self-citationSRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · see citing works
The PARP Side of the Nucleus: Molecular Actions, Physiological Outcomes, and Clinical Targets
Krishnakumar, R., & Kraus, W. L. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.017 · Cited by 836 · see citing works
Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · see citing works
Self-citationDiabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation
Soriano, F. G., Virág, L., Jagtap, P. G., Szabó, É., Mabley, J. G., Liaudet, L., Marton, A., Hoyt, D. G., Murthy, K. G. K., Salzman, A. L., et al. (2001) · Nature Medicine · doi:10.1038/83241 · Cited by 602 · see citing works
Schraufstätter, I. U., Hinshaw, D. B., Hyslop, P. A., Spragg, R. G., & Cochrane, C. G. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112436 · Cited by 511 · see citing works
Pillai, J. B., Isbatan, A., Imai, S., & Gupta, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506162200 · Cited by 391 · see citing works
Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding
Asher, G., Reinke, H., Altmeyer, M., Gutierrez-Arcelus, M., Hottiger, M. O., & Schibler, U. (2010) · Cell · doi:10.1016/j.cell.2010.08.016 · Cited by 340 · see citing works
Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress
Chua, K. F., Mostoslavsky, R., Lombard, D. B., Pang, W. W., Saito, S., Franco, S., Kaushal, D., Cheng, H.-L., Fischer, M. R., Stokes, N., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.007 · Cited by 257 · see citing works
Barbosa, M. T., Soares, S. M., Novak, C. M., Sinclair, D. A., Levine, J. A., Aksoy, P., & Chini, E. N. (2007) · The FASEB Journal · doi:10.1096/fj.07-8290com · Cited by 249 · see citing works
Kolthur‐Seetharam, U., Dantzer, F., McBurney, M. W., de MURCIA, G., & Sassone‐Corsi, P. (2006) · Cell Cycle · doi:10.4161/cc.5.8.2690 · Cited by 203 · 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
Self-citationAksoy, P., Escande, C., White, T. A., Thompson, M., Soares, S. M., Benech, J. C., & Chini, E. N. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.066 · Cited by 173 · see citing works
Chemical Activation of Sir2-Dependent Silencing by Relief of Nicotinamide Inhibition
Sauve, A. A., Moir, R. D., Schramm, V. L., & Willis, I. M. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.032 · Cited by 144 · see citing works
Self-citationA continuous microplate assay for sirtuins and nicotinamide-producing enzymes
Smith, B. C., Hallows, W. C., & Denu, J. M. (2009) · Analytical Biochemistry · doi:10.1016/j.ab.2009.07.019 · Cited by 141 · see citing works
Dali‐Youcef, N., Mataki, C., Coste, A., Messaddeq, N., Giroud, S., Blanc, S., Koehl, C., Champy, M., Chambon, P., Lluis Fajas, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611568104 · Cited by 115 · see citing works
Self-citationBai, P., Houten, S. M., Huber, A., Schreiber, V., 渡辺, 光., Kiss, B., de MURCIA, G., Auwerx, J. H., & Murcia, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701021200 · Cited by 105 · see citing works
Self-citationErdélyi, K., Bai, P., Kovács, I., Szabó, É., Mocsár, G., Kakuk, A., Szabó, C., Gergely, P., & Virág, L. (2009) · The FASEB Journal · doi:10.1096/fj.09-133264 · Cited by 95 · see citing works
Self-citationAllinson, S. L., Dianova, I. I., & Dianov, G. L. (2003) · Acta Biochimica Polonica · doi:10.18388/abp.2003_3724 · Cited by 94 · see citing works
Adamietz, P. (1987) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1987.tb13621.x · Cited by 66 · see citing works
PARP1 deficiency exacerbates diet-induced obesity in mice
Devalaraja-Narashimha, K. B., & Padanilam, B. J. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0402 · Cited by 64 · see citing works
Effects of nicotinamide on NAD and poly (ADP‐ribose) metabolism in DNA‐damaged human lymphocytes
Sims, J. L., Berger, S. J., & Berger, N. A. (1981) · Journal of Supramolecular Structure and Cellular Biochemistry · doi:10.1002/jsscb.1981.380160308 · Cited by 45 · see citing works
Knight, M. I., & Chambers, P. J. (2001) · Protein Expression and Purification · doi:10.1006/prep.2001.1513 · Cited by 13 · see citing works
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Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
Self-citationCantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
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Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
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Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481 · see citing works
NAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · see citing works
Self-citationMouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210 · see citing works
Self-citationNAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901 · see citing works
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Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865 · see citing works
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Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787 · see citing works
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Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752 · see citing works
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Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD+/SIRT1 Reduction
Fang, E. F., Scheibye-Knudsen, M., Brace, L. E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J. R., Croteau, D. L., & Bohr, V. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.026 · Cited by 711 · see citing works
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NAD+ homeostasis in health and disease
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Self-citationMammalian Mitochondria and Aging: An Update
Kauppila, T. E. S., Kauppila, J. H. K., & Larsson, N.-G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.017 · Cited by 578 · see citing works
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
Self-citationImpairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496 · see citing works
“During aging, the level of NAD+ declines in many tissues, in part, due to increased activity of the NAD-consuming enzymes CD38 and PARP1 (Bai et al., 2011b; Camacho-Pereira et al., 2016; Li et al., 2017; Mouchiroud et al., 2013).”
NAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
Redox regulation of SIRT1 in inflammation and cellular senescence
Hwang, J.-W., Yao, H., Caito, S., Sundar, I. K., & Rahman, I. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.015 · Cited by 503 · see citing works
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Tarragó, M. G., Chini, C. C. S., Kanamori, K. S., Warner, G. M., Caride, A., de Oliveira, G. C., Rud, M., Samani, A., Hein, K. Z., Huang, R., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.016 · Cited by 384 · see citing works
Nuclear DNA damage signalling to mitochondria in ageing
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Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
Self-citationLi, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360 · see citing works
NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease
Cerutti, R., Pirinen, E., Lamperti, C., Marchet, S., Sauve, A. A., Li, W., Leoni, V., Schon, E. A., Dantzer, F., Auwerx, J., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.001 · Cited by 343 · see citing works
“Nicotinamide Riboside was custom synthesized by Novalix, France.”
Self-citationGui, D. Y., Sullivan, L. B., Luengo, A., Hosios, A. M., Bush, L. N., Gitego, N., Davidson, S. M., Freinkman, E., Thomas, C. J., & Vander Heiden, M. G. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.006 · Cited by 323 · see citing works
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Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013) · Diabetes · doi:10.2337/db12-1139 · Cited by 332 · see citing works
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Self-citationDNA damage response and metabolic disease
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Poly(ADP-ribose) signaling in cell death
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Pirinen, 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 · see citing works
“These observations are in line with observations in Parp-1 / mice, where SIRT1, but not SIRT3, activity was enhanced (Bai et al., 2011).”
BackgroundResultInfluentialSelf-citationRyu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A. G., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf5504 · Cited by 256 · see citing works
Self-citationCoordination of DNA single strand break repair
Abbotts, R., & Wilson, D. M. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.039 · Cited by 240 · see citing works
Crosstalk 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
Self-citationGuan, Y., Wang, S.-R., Huang, X.-Z., Xie, Q.-H., Xu, Y.-Y., Shang, D., & Hao, C.-M. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016040385 · Cited by 238 · see citing works
NAD and the aging process: role in life, death and everything in between
Chini, C. C. S., Tarragó, M. G., & Chini, E. N. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.11.003 · Cited by 208 · 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
“The effects of Parp1 deletion were due to elevation of NAD+ levels and subsequent SIRT1-dependent activation of mitochondrial metabolism in brown adipose tissue and muscle (Bai et al., 2011b).”
BackgroundInfluentialSelf-citationNAD+ biosynthesis, aging, and disease
Johnson, S., & Imai, S. (2018) · F1000Research · doi:10.12688/f1000research.12120.1 · Cited by 178 · see citing works
Santos, A. L., Sinha, S., & Lindner, A. B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1941285 · Cited by 168 · see citing works
SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation
Hayakawa, T., Iwai, M., Aoki, S., Takimoto, K., Maruyama, M., Maruyama, W., & Motoyama, N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0116480 · Cited by 170 · see citing works
The role of PARP1 in neurodegenerative diseases and aging
Mao, K., & Zhang, G. (2022) · The FEBS Journal · doi:10.1111/febs.15716 · Cited by 172 · see citing works
Gariani, K., Ryu, D., Menzies, K. J., Yi, H.-S., Stein, S., Zhang, H., Perino, A., Lemos, V., Katsyuba, E., Jha, P., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.08.024 · Cited by 167 · see citing works
“The hyperactivation of PARPs can initiate the programmed cell death pathway causing both ATP and nicotinamide adenine dinucleotide (NAD) depletion [22], which reduces mitochondrial function and b-oxidation of fats [18,19,21,23].”
BackgroundMethodSelf-citationA model of the mitochondrial basis of bipolar disorder
Morris, G., Walder, K., McGee, S. L., Dean, O. M., Tye, S. J., Maes, M., & Berk, M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.014 · Cited by 162 · see citing works
Tipping the metabolic scales towards increased longevity in mammals
Riera, C. E., & Dillin, A. (2015) · Nature Cell Biology · doi:10.1038/ncb3107 · Cited by 153 · see citing works
Dollerup, O. L., Chubanava, S., Agerholm, M., Søndergård, S. D., Altıntaş, A., Møller, A. B., Høyer, K. F., Ringgaard, S., Stødkilde‐Jørgensen, H., Lavery, G. G., et al. (2020) · The Journal of Physiology · doi:10.1113/jp278752 · Cited by 145 · see citing works
Why NAD + Declines during Aging: It’s Destroyed
Schultz, M. B., & Sinclair, D. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.022 · Cited by 126 · see citing works
Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation
Cuyàs, E., Verdura, S., Llorach-Parés, L., Fernández-Arroyo, S., Joven, J., Martin-Castillo, B., Bosch-Barrera, J., Brunet, J., Nonell-Canals, A., Sanchez-Martinez, M., et al. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00657 · Cited by 122 · see citing works
NAD+ flux is maintained in aged mice despite lower tissue concentrations
McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.001 · Cited by 112 · see citing works
Xu, Y., Yu, T., Ma, G., Zheng, L., Jiang, X., Yang, F., Wang, Z., Li, N., He, Z., Song, X., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.62556 · Cited by 110 · see citing works
Metabolic effects of resveratrol: Addressing the controversies
Bitterman, J. L., & Chung, J. H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1808-8 · Cited by 109 · see citing works
Harlan, B. A., Pehar, M., Sharma, D. R., Beeson, G., Beeson, C. C., & Vargas, M. R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.698779 · Cited by 94 · see citing works
Regulation of SIRT1 activity by genotoxic stress
Yuan, J., Luo, K., Liu, T., & Lou, Z. (2012) · Genes & Development · doi:10.1101/gad.188482.112 · Cited by 79 · see citing works
Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation
Sahar, S., Nin, V., Barbosa, M. T., Chini, E. N., & Sassone-Corsi, P. (2011) · Aging · doi:10.18632/aging.100368 · Cited by 79 · see citing works
Fischer, J. M. F., Popp, O., Gebhard, D., Veith, S., Fischbach, A., Beneke, S., Leitenstorfer, A., Bergemann, J., Scheffner, M., Ferrando‐May, E., et al. (2014) · The FEBS Journal · doi:10.1111/febs.12885 · Cited by 72 · see citing works
Ruggieri, S., Orsomando, G., Sorci, L., & Raffaelli, N. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.02.021 · Cited by 71 · see citing works
Lehmann, S., Costa, A. C., Celardo, I., Loh, S. H. Y., & Martins, L. M. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.72 · Cited by 69 · see citing works
“Conversely, the knockout of Parp-1 in mice or its worm orthologue, pme-1, is reported to result in an increase in NAD levels.(10,38) This suggests that the total depletion of this NAD-consuming enzyme improves the availability of this metabolite for other enzymatic reactions.”
BackgroundNAD+ in COVID-19 and viral infections
Zheng, M., Schultz, M. B., & Sinclair, D. A. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.02.001 · Cited by 62 · see citing works
Shi, W., Hegeman, M. A., van Dartel, D. A. M., Tang, J., Suarez, M., Swarts, H., van der Hee, B., Arola, L., & Keijer, J. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600878 · Cited by 62 · see citing works
Lloret, A., & Beal, M. F. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02809-1 · Cited by 52 · see citing works
Harlan, B. A., Pehar, M., Killoy, K. M., & Vargas, M. R. (2019) · The FASEB Journal · doi:10.1096/fj.201802752r · Cited by 50 · see citing works
Erener, S., Mirsaidi, A., Hesse, M., Tiaden, A. N., Ellingsgaard, H., Kostadinova, R., Donath, M. Y., Richards, P. J., & Hottiger, M. O. (2012) · The FASEB Journal · doi:10.1096/fj.11-200212 · Cited by 48 · see citing works
Ren, Z., Xu, Y., Li, T., Sun, W., Tang, Z., Wang, Y., Zhou, K., Li, J., Ding, Q., Liang, K., et al. (2022) · Animal Nutrition · doi:10.1016/j.aninu.2022.06.009 · Cited by 44 · see citing works
Poly (ADP-ribose) polymerase 1 and neurodegenerative diseases: past, present, and future
Hu, M.-L., Pan, Y.-R., Yong, Y.-Y., Liu, Y., Yu, L., Qin, D.-L., Qiao, G., Law, B. Y.-K., Wu, J.-M., Zhou, X.-G., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102078 · Cited by 44 · see citing works
Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress
Xu, R., Yuan, Z., Yang, L., Li, L., Li, D., & Lv, C. (2017) · Oncology Reports · doi:10.3892/or.2017.5793 · Cited by 36 · see citing works
Sirtuin activation as a therapeutic approach against inborn errors of metabolism
Bleeker, J. C., & Houtkooper, R. H. (2016) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-016-9939-8 · Cited by 11 · see citing works
Self-citationMitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2 · see citing works
- Authors
- Bai, P., Cantó, C., Oudart, H., Brunyánszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R. H., Schoonjans, K., Schreiber, V., Sauve, A. A., Menissier-de Murcia, J., & Auwerx, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- University of Debrecen (HU)
- Weill Cornell Medicine (US)
- Corresponding author
- Auwerx, Johan
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 13
- Issue
- 4
- Pages
- 461-468
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3086520
- OpenAlex
- W2020304127
- Cited by
- 837
- References
- 36
- Citations by year
- 2026: 51 · 2025: 49 · 2024: 49 · 2023: 49 · 2022: 60 · 2021: 69 · 2020: 67 · 2019: 61 · 2018: 52 · 2017: 72 · 2016: 60 · 2015: 52 · 2014: 44 · 2013: 47 · 2012: 39
- FWCI
- 22.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion)
- univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-59820, R01DK073466, DK73466, P01DK059820)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PARP1 inhibition, SIRT1 activation, mitochondrial metabolism, brown adipose tissue, skeletal muscle, energy expenditure, metabolic disorders, oxidative metabolism, PARP-1 knockout mice, cancer metabolism
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Poly (ADP-Ribose) Polymerase-1, Animals, Adipose Tissue, Brown, Energy Metabolism, Mitochondria, NAD, Phenotype, Poly(ADP-ribose) Polymerases, Mice, Knockout, Oxidative Stress, Muscle, Skeletal, RNA Interference, RNA, Small Interfering, Mice, Sirtuin 1
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