Skip to main content
Log in

Role of NUDIX Hydrolases in NAD and ADP-Ribose Metabolism in Mammals

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Proteins of the NUDIX hydrolase (NUDT) superfamily that cleave organic pyrophosphates are found in all classes of organisms, from archaea and bacteria to higher eukaryotes. In mammals, NUDTs exhibit a wide range of functions and are characterized by different substrate specificity and intracellular localization. They control the concentration of various metabolites in the cell, including key regulatory molecules such as nicotinamide adenine dinucleotide (NAD), ADP-ribose, and their derivatives. In this review, we discuss the role of NUDT proteins in the metabolism of NAD and ADP-ribose in human and animal cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

Abbreviations

ADPR:

ADP-ribose

AMPK:

AMP-activated protein kinase

ANT:

adenine nucleotide translocase

ARH:

ADP-ribosylhydrolase

cADPR:

cyclic ADP-ribose

ER:

endoplasmic reticulum

Nam:

nicotinamide

NAD:

nicotinamide adenine dinucleotide

NADP:

nicotinamide adenine dinucleotide phosphate

NMN:

nicotinamide mononucleotide

NMNAT:

nicotinamide mononucleotide adenylyltransferase

NUDT:

NUDIX hydrolase

OAcADPR:

O-acetyl-ADP-ribose

PARP:

poly(ADP-ribose) polymerase

PAR:

poly(ADP-ribose)

PARG:

poly(ADP-ribose) glycohydrolase

R5′P:

ribose 5′-phosphate

ROS:

reactive oxygen species

TARG:

terminal ADP-ribose protein glycohydrolase 1

REFERENCES

  1. McLennan, A. G. (2006) The Nudix hydrolase superfamily, Cell. Mol. Life Sci., 63, 123-143, doi: https://doi.org/10.1007/s00018-005-5386-7.

    Article  CAS  PubMed  Google Scholar 

  2. Carreras-Puigvert, J., Zitnik, M., Jemth, A. S., Carter, M., Unterlass, J. E. et al. (2017) A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family, Nat. Commun., 8, 1541, doi: https://doi.org/10.1038/s41467-017-01642-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rai, P., and Sobol, R. W. (2019) Mechanisms of MTH1 inhibition-induced DNA strand breaks: the slippery slope from the oxidized nucleotide pool to genotoxic damage, DNA Rep., 77, 18-26, doi: https://doi.org/10.1016/j.dnarep.2019.03.001.

    Article  CAS  Google Scholar 

  4. Ishibashi, T., Hayakawa, H., and Sekiguchi, M. (2003) A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides, EMBO Rep., 4, 479-483, doi: https://doi.org/10.1038/sj.embor.embor838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cai, J. P., Ishibashi, T., Takagi, Y., Hayakawa, H., and Sekiguchi, M. (2003) Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides, Biochem. Biophys. Res. Commun., 305, 1073-1077, doi: https://doi.org/10.1016/s0006-291x(03)00864-7.

    Article  CAS  PubMed  Google Scholar 

  6. Ishibashi, T., Hayakawa, H., Ito, R., Miyazawa, M., Yamagata, Y., and Sekiguchi, M. (2005) Mammalian enzymes for preventing transcriptional errors caused by oxidative damage, Nucleic Acids Res., 33, 3779-3784, doi: https://doi.org/10.1093/nar/gki682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Grudzien-Nogalska, E., and Kiledjian, M. (2017) New insights into decapping enzymes and selective mRNA decay, Wiley Interdisc. Rev. RNA, 8, doi: https://doi.org/10.1002/wrna.1379.

    Article  Google Scholar 

  8. Lu, G., Zhang, J., Li, Y., Li, Z., Zhang, N., Xu, X., Wang, T., Guan, Z., Gao, G. F., and Yan, J. (2011) hNUDT16: a universal decapping enzyme for small nucleolar RNA and cytoplasmic mRNA, Protein Cell, 2, 64-73, doi: https://doi.org/10.1007/s13238-011-1009-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gasmi, L., and McLennan, A. G. (2001) The mouse Nudt7 gene encodes a peroxisomal nudix hydrolase specific for coenzyme A and its derivatives, Biochem. J., 357, 33-38, doi: https://doi.org/10.1042/0264-6021:3570033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shumar, S. A., Kerr, E. W., Geldenhuys, W. J., Montgomery, G. E., Fagone, P., Thirawatananond, P., Saavedra, H., Gabelli, S. B., and Leonardi, R. (2018) Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform, J. Biol. Chem., 293, 4134-4148, doi: https://doi.org/10.1074/jbc.RA117.001358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kerr, E. W., Shumar, S. A., and Leonardi, R. (2019) Nudt8 is a novel CoA diphosphohydrolase that resides in the mitochondria, FEBS Lett., 593, 1133-1143, doi: https://doi.org/10.1002/1873-3468.13392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ying, W. (2008) NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences, Antioxid. Redox Signal., 10, 179-206, doi: https://doi.org/10.1089/ars.2007.1672.

    Article  CAS  PubMed  Google Scholar 

  13. Kulikova, V. A., Gromyko, D. V., and Nikiforov, A. A. (2018) The regulatory role of NAD in human and animal cells, Biochemistry (Moscow), 83, 800-812, doi: https://doi.org/10.1134/S0006297918070040.

    Article  CAS  Google Scholar 

  14. Stromland, O., Niere, M., Nikiforov, A. A., VanLinden, M. R., Heiland, I., and Ziegler, M. (2019) Keeping the balance in NAD metabolism, Biochem. Soc. Trans., 47, 119-130, doi: https://doi.org/10.1042/BST20180417.

    Article  PubMed  Google Scholar 

  15. Yang, Y., and Sauve, A. A. (2016) NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy, Biochim. Biophys. Acta, 1864, 1787-1800, doi: https://doi.org/10.1016/j.bbapap.2016.06.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gupte, R., Liu, Z., and Kraus, W. L. (2017) PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes, Genes Dev., 31, 101-126, doi: https://doi.org/10.1101/gad.291518.116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cohen, M. S., and Chang, P. (2018) Insights into the biogenesis, function, and regulation of ADP-ribosylation, Nat. Chem. Biol., 14, 236-243, doi: https://doi.org/10.1038/nchembio.2568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rack, J. G. M., Palazzo, L., and Ahel, I. (2020) (ADP-ribosyl)hydrolases: structure, function, and biology, Genes Dev., 34, 263-284, doi: https://doi.org/10.1101/gad.334631.119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Talhaoui, I., Lebedeva, N. A., Zarkovic, G., Saint-Pierre, C., Kutuzov, M. M., Sukhanova, M. V., Matkarimov, B. T., Gasparutto, D., Saparbaev, M. K., Lavrik, O. I., and Ishchenko, A. A. (2016) Poly(ADP-ribose) polymerases covalently modify strand break termini in DNA fragments in vitro, Nucleic Acids Res., 44, 9279-9295, doi: https://doi.org/10.1093/nar/gkw675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Munnur, D., and Ahel, I. (2017) Reversible mono-ADP-ribosylation of DNA breaks, FEBS J., 284, 4002-4016, doi: https://doi.org/10.1111/febs.14297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Munnur, D., Bartlett, E., Mikolcevic, P., Kirby, I. T., Rack, J. G. M., Mikoc, A., Cohen, M. S., and Ahel, I. (2019) Reversible ADP-ribosylation of RNA, Nucleic Acids Res., 47, 5658-5669, doi: https://doi.org/10.1093/nar/gkz305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Houtkooper, R. H., Pirinen, E., and Auwerx, J. (2012) Sirtuins as regulators of metabolism and healthspan, Nat. Rev. Mol. Cell Biol., 13, 225-238, doi: https://doi.org/10.1038/nrm3293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tanner, K. G., Landry, J., Sternglanz, R., and Denu, J. M. (2000) Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose, Proc. Natl. Acad. Sci. USA, 97, 14178-14182, doi: https://doi.org/10.1073/pnas.250422697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sassone-Corsi, P. (2016) The Epigenetic and Metabolic Language of the Circadian Clock, in A Time for Metabolism and Hormones (Sassone-Corsi, P., and Christen, Y., eds.) Cham (CH), pp. 1-11.

  25. Imai, S., and Guarente, L. (2014) NAD+ and sirtuins in aging and disease, Trends Cell. Biol., 24, 464-471, doi: https://doi.org/10.1016/j.tcb.2014.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cao, Y., Jiang, X., Ma, H., Wang, Y., Xue, P., and Liu, Y. (2016) SIRT1 and insulin resistance, J. Diabetes Complic., 30, 178-183, doi: https://doi.org/10.1016/j.jdiacomp.2015.08.022.

    Article  Google Scholar 

  27. Grubisha, O., Rafty, L. A., Takanishi, C. L., Xu, X., Tong, L., Perraud, A. L., Scharenberg, A. M., and Denu, J. M. (2006) Metabolite of SIR2 reaction modulates TRPM2 ion channel, J. Biolog. Chem., 281, 14057-14065, doi: https://doi.org/10.1074/jbc.M513741200.

    Article  CAS  Google Scholar 

  28. Chen, D., Vollmar, M., Rossi, M. N., Phillips, C., Kraehenbuehl, R., Slade, D., Mehrotra, P. V., von Delft, F., Crosthwaite, S. K., Gileadi, O., Denu, J. M., and Ahel, I. (2011) Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases, J. Biolog. Chem., 286, 13261-13271, doi: https://doi.org/10.1074/jbc.M110.206771.

    Article  CAS  Google Scholar 

  29. Ono, T., Kasamatsu, A., Oka, S., and Moss, J. (2006) The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases, Proc. Natl. Acad. Sci. USA, 103, 16687-16691, doi: https://doi.org/10.1073/pnas.0607911103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee, H. C., and Zhao, Y. J. (2019) Resolving the topological enigma in Ca2+ signaling by cyclic ADP-ribose and NAADP, J. Biolog. Chem., 294, 19831-19843, doi: https://doi.org/10.1074/jbc.REV119.009635.

    Article  CAS  Google Scholar 

  31. Guse, A. H. (2015) Calcium mobilizing second messengers derived from NAD, Biochim. Biophys. Acta, 1854, 1132-1137, doi: https://doi.org/10.1016/j.bbapap.2014.12.015.

    Article  CAS  PubMed  Google Scholar 

  32. Sumoza-Toledo, A., and Penner, R. (2011) TRPM2: a multifunctional ion channel for calcium signalling, J. Physiol., 589, 1515-1525, doi: https://doi.org/10.1113/jphysiol.2010.201855.

    Article  CAS  PubMed  Google Scholar 

  33. Jiao, X., Doamekpor, S. K., Bird, J. G., Nickels, B. E., Tong, L., Hart, R. P., and Kiledjian, M. (2017) 5′-End nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding, Cell, 168, 1015-1027, doi: https://doi.org/10.1016/j.cell.2017.02.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Luscher, B., Butepage, M., Eckei, L., Krieg, S., Verheugd, P., and Shilton, B. H. (2018) ADP-ribosylation, a multifaceted posttranslational modification involved in the control of cell physiology in health and disease, Chem. Rev., 118, 1092-1136, doi: https://doi.org/10.1021/acs.chemrev.7b00122.

    Article  CAS  PubMed  Google Scholar 

  35. Nikiforov, A., Kulikova, V., and Ziegler, M. (2015) The human NAD metabolome: functions, metabolism and compartmentalization, Crit. Rev. Biochem. Mol. Biol., 50, 284-297, doi: https://doi.org/10.3109/10409238.2015.1028612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Katsyuba, E., Romani, M., Hofer, D., and Auwerx, J. (2020) NAD+ homeostasis in health and disease, Nat. Metab., 2, doi: https://doi.org/10.1038/s42255-019-0161-5.

    Article  Google Scholar 

  37. Dolle, C., Skoge, R. H., Vanlinden, M. R., and Ziegler, M. (2013) NAD biosynthesis in humans – enzymes, metabolites and therapeutic aspects, Curr. Top. Med. Chem., 13, 2907-2917, doi: https://doi.org/10.2174/15680266113136660206.

    Article  CAS  PubMed  Google Scholar 

  38. Yang, Y., Zhang, N., Zhang, G., and Sauve, A. A. (2020) NRH salvage and conversion to NAD+ requires NRH kinase activity by adenosine kinase, Nat. Metab., 2, 364-379, doi: https://doi.org/10.1038/s42255-020-0194-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Frick, D. N., and Bessman, M. J. (1995) Cloning, purification, and properties of a novel NADH pyrophosphatase. Evidence for a nucleotide pyrophosphatase catalytic domain in MutT-like enzymes, J. Biolog. Chem., 270, 1529-1534, doi: https://doi.org/10.1074/jbc.270.4.1529.

    Article  CAS  Google Scholar 

  40. Shimizu, M., Masuo, S., Fujita, T., Doi, Y., Kamimura, Y., and Takaya, N. (2012) Hydrolase controls cellular NAD, sirtuin, and secondary metabolites, Mol. Cell. Biol., 32, 3743-3755, doi: https://doi.org/10.1128/MCB.00032-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xu, W., Dunn, C. A., and Bessman, M. J. (2000) Cloning and characterization of the NADH pyrophosphatases from Caenorhabditis elegans and Saccharomyces cerevisiae, members of a Nudix hydrolase subfamily, Biochem. Biophys. Res. Commun., 273, 753-758, doi: https://doi.org/10.1006/bbrc.2000.2999.

    Article  CAS  PubMed  Google Scholar 

  42. AbdelRaheim, S. R., Cartwright, J. L., Gasmi, L., and McLennan, A. G. (2001) The NADH diphosphatase encoded by the Saccharomyces cerevisiae NPY1 Nudix hydrolase gene is located in peroxisomes, Arch. Biochem. Biophys., 388, 18-24, doi: https://doi.org/10.1006/abbi.2000.2268.

    Article  CAS  PubMed  Google Scholar 

  43. AbdelRaheim, S. R., Spiller, D. G., and McLennan, A. G. (2003) Mammalian NADH diphosphatases of the Nudix family: cloning and characterization of the human peroxisomal NUDT12 protein, Biochem. J., 374, 329-335, doi: https://doi.org/10.1042/BJ20030441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dunn, C. A., O’Handley, S. F., Frick, D. N., and Bessman, M. J. (1999) Studies on the ADP-ribose pyrophosphatase subfamily of the nudix hydrolases and tentative identification of trgB, a gene associated with tellurite resistance, J. Biol. Chem., 274, 32318-32324, doi: https://doi.org/10.1074/jbc.274.45.32318.

    Article  CAS  PubMed  Google Scholar 

  45. Lin, S., Gasmi, L., Xie, Y., Ying, K., Gu, S., Wang, Z., Jin, H., Chao, Y., Wu, C., Zhou, Z., Tang, R., Mao, Y., and McLennan, A. G. (2002) Cloning, expression and characterisation of a human Nudix hydrolase specific for adenosine 5′-diphosphoribose (ADP-ribose), Biochim. Biophys. Acta, 1594, 127-135, doi: https://doi.org/10.1016/s0167-4838(01)00296-5.

    Article  CAS  PubMed  Google Scholar 

  46. Tong, L., Lee, S., and Denu, J. M. (2009) Hydrolase regulates NAD+ metabolites and modulates cellular redox, J. Biol. Chem., 284, 11256-11266, doi: https://doi.org/10.1074/jbc.M809790200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Adam-Vizi, V., and Chinopoulos, C. (2006) Bioenergetics and the formation of mitochondrial reactive oxygen species, Trends Pharmacol. Sci., 27, 639-645, doi: https://doi.org/10.1016/j.tips.2006.10.005.

    Article  CAS  PubMed  Google Scholar 

  48. Jamieson, D. J. (1998) Oxidative stress responses of the yeast Saccharomyces cerevisiae, Yeast, 14, 1511-1527, doi: https://doi.org/10.1002/(SICI)1097-0061(199812)14:16<1511::AID-YEA356>3.0.CO;2-S.

    Article  CAS  PubMed  Google Scholar 

  49. Abdelraheim, S. R., Spiller, D. G., and McLennan, A. G. (2017) Mouse Nudt13 is a mitochondrial Nudix hydrolase with NAD(P)H pyrophosphohydrolase activity, Protein J., 36, 425-432, doi: https://doi.org/10.1007/s10930-017-9734-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wu, H., Li, L., Chen, K. M., Homolka, D., Gos, P., Fleury-Olela, F., McCarthy, A. A., and Pillai, R. S. (2019) Decapping enzyme NUDT12 partners with BLMH for cytoplasmic surveillance of NAD-capped RNAs, Cell Rep., 29, 4422-4434, doi: https://doi.org/10.1016/j.celrep.2019.11.108.

    Article  CAS  PubMed  Google Scholar 

  51. Wanders, R. J., Waterham, H. R., and Ferdinandusse, S. (2015) Metabolic interplay between peroxisomes and other subcellular organelles including mitochondria and the endoplasmic reticulum, Front. Cell Dev. Biol., 3, 83, doi: https://doi.org/10.3389/fcell.2015.00083.

    Article  PubMed  Google Scholar 

  52. Agrimi, G., Russo, A., Scarcia, P., and Palmieri, F. (2012) The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+, Biochem. J., 443, 241-247, doi: https://doi.org/10.1042/BJ20111420.

    Article  CAS  PubMed  Google Scholar 

  53. Antonenkov, V. D., and Hiltunen, J. K. (2012) Transfer of metabolites across the peroxisomal membrane, Biochim. Biophys. Acta, 1822, 1374-1386, doi: https://doi.org/10.1016/j.bbadis.2011.12.011.

    Article  CAS  PubMed  Google Scholar 

  54. Antonenkov, V. D., Sormunen, R. T., and Hiltunen, J. K. (2004) The rat liver peroxisomal membrane forms a permeability barrier for cofactors but not for small metabolites in vitro, J. Cell Sci., 117, 5633-5642, doi: https://doi.org/10.1242/jcs.01485.

    Article  CAS  PubMed  Google Scholar 

  55. Rokka, A., Antonenkov, V. D., Soininen, R., Immonen, H. L., Pirila, P. L., Bergmann, U., Sormunen, R. T., Weckstrom, M., Benz, R., and Hiltunen, J. K. (2009) Pxmp2 is a channel-forming protein in Mammalian peroxisomal membrane, PLoS One, 4, e5090, doi: https://doi.org/10.1371/journal.pone.0005090.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ramanathan, A., Robb, G. B., and Chan, S. H. (2016) mRNA capping: biological functions and applications, Nucleic Acids Res., 44, 7511-7526, doi: https://doi.org/10.1093/nar/gkw551.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Grudzien-Nogalska, E., Wu, Y., Jiao, X., Cui, H., Mateyak, M. K., Hart, R. P., Tong, L., and Kiledjian, M. (2019) Structural and mechanistic basis of mammalian Nudt12 RNA deNADding, Nat. Chem. Biol., 15, 575-582, doi: https://doi.org/10.1038/s41589-019-0293-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Alano, C. C., Tran, A., Tao, R., Ying, W., Karliner, J. S., and Swanson, R. A. (2007) Differences among cell types in NAD(+) compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes, J. Neurosci. Res., 85, 3378-3385, doi: https://doi.org/10.1002/jnr.21479.

    Article  CAS  PubMed  Google Scholar 

  59. Stein, L. R., and Imai, S. (2012) The dynamic regulation of NAD metabolism in mitochondria, Trends Edocrinol. Metab., 23, 420-428, doi: https://doi.org/10.1016/j.tem.2012.06.005.

    Article  CAS  Google Scholar 

  60. Wallace, D. C. (2009) Mitochondria, bioenergetics, and the epigenome in eukaryotic and human evolution, Cold Spring Harb. Symp. Quant. Biol., 74, 383-393, doi: https://doi.org/10.1101/sqb.2009.74.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dolle, C., Rack, J. G., and Ziegler, M. (2013) NAD and ADP-ribose metabolism in mitochondria, FEBS J., 280, 3530-3541, doi: https://doi.org/10.1111/febs.12304.

    Article  CAS  PubMed  Google Scholar 

  62. 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., de Cabo, R., Sauve, A. A., and Sinclair, D. A. (2007) Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival, Cell, 130, 1095-1107, doi: https://doi.org/10.1016/j.cell.2007.07.035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pittelli, M., Formentini, L., Faraco, G., Lapucci, A., Rapizzi, E., Cialdai, F., Romano, G., Moneti, G., Moroni, F., and Chiarugi, A. (2010) Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool, J. Biol. Chem., 285, 34106-34114, doi: https://doi.org/10.1074/jbc.M110.136739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Barile, M., Passarella, S., Danese, G., and Quagliariello, E. (1996) Rat liver mitochondria can synthesize nicotinamide adenine dinucleotide from nicotinamide mononucleotide and ATP via a putative matrix nicotinamide mononucleotide adenylyltransferase, Biochem. Mol. Biol. Intern., 38, 297-306.

    CAS  Google Scholar 

  65. Nikiforov, A., Dolle, C., Niere, M., and Ziegler, M. (2011) Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation, J. Biol. Chem., 286, 21767-21778, doi: https://doi.org/10.1074/jbc.M110.213298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Davila, A., Liu, L., Chellappa, K., Redpath, P., Nakamaru-Ogiso, E., Paolella, L. M., Zhang, Z., Migaud, M. E., Rabinowitz, J. D., and Baur, J. A. (2018) Nicotinamide adenine dinucleotide is transported into mammalian mitochondria, Elife, 7, doi: https://doi.org/10.7554/eLife.33246.

    Article  Google Scholar 

  67. Cambronne, X. A., Stewart, M. L., Kim, D., Jones-Brunette, A. M., Morgan, R. K., Farrens, D. L., Cohen, M. S., and Goodman, R. H. (2016) Biosensor reveals multiple sources for mitochondrial NAD(+), Science, 352, 1474-1477, doi: https://doi.org/10.1126/science.aad5168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sharma, S., Grudzien-Nogalska, E., Hamilton, K., Jiao, X., Yang, J., Tong, L., and Kiledjian, M. (2020) Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs, Nucleic Acids Res., 48, 6788-6798, doi: https://doi.org/10.1093/nar/gkaa402.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Wright, R. H., Lioutas, A., Le Dily, F., Soronellas, D., Pohl, A., Bonet, J., Nacht, A. S., Samino, S., Font-Mateu, J., Vicent, G. P., Wierer, M., Trabado, M. A., Schelhorn, C., Carolis, C., Macias, M. J., Yanes, O., Oliva, B., and Beato, M. (2016) ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling, Science, 352, 1221-1225, doi: https://doi.org/10.1126/science.aad9335.

    Article  CAS  PubMed  Google Scholar 

  70. Gasmi, L., Cartwright, J. L., and McLennan, A. G. (1999) Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif, Biochem. J., 344 Pt. 2, 331-337.

    Article  PubMed  Google Scholar 

  71. Page, B. D. G., Valerie, N. C. K., Wright, R. H. G., Wallner, O., Isaksson, R., Carter, M., Rudd, S. G., Loseva, O., Jemth, A. S., Almlof, I., Font-Mateu, J., Llona-Minguez, S., Baranczewski, P., Jeppsson, F., Homan, E., Almqvist, H., Axelsson, H., Regmi, S., Gustavsson, A. L., Lundback, T. et al. (2018) Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells, Nat. Commun., 9, 250, doi: https://doi.org/10.1038/s41467-017-02293-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Yoon, B., Yang, E. G., and Kim, S. Y. (2018) The ADP-ribose reactive NUDIX hydrolase isoforms can modulate HIF-1alpha in cancer cells, Biochem. Biophys. Res. Commun., 504, 321-327, doi: https://doi.org/10.1016/j.bbrc.2018.08.185.

    Article  CAS  PubMed  Google Scholar 

  73. Formentini, L., Macchiarulo, A., Cipriani, G., Camaioni, E., Rapizzi, E., Pellicciari, R., Moroni, F., and Chiarugi, A. (2009) Poly(ADP-ribose) catabolism triggers AMP-dependent mitochondrial energy failure, J. Biol. Chem., 284, 17668-17676, doi: https://doi.org/10.1074/jbc.M109.002931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Nury, H., Dahout-Gonzalez, C., Trezeguet, V., Lauquin, G. J., Brandolin, G., and Pebay-Peyroula, E. (2006) Relations between structure and function of the mitochondrial ADP/ATP carrier, Annu. Rev. Biochem., 75, 713-741, doi: https://doi.org/10.1146/annurev.biochem.75.103004.142747.

    Article  CAS  PubMed  Google Scholar 

  75. Hardie, D. G., Ross, F. A., and Hawley, S. A. (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol., 13, 251-262, doi: https://doi.org/10.1038/nrm3311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Gowans, G. J., Hawley, S. A., Ross, F. A., and Hardie, D. G. (2013) AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab., 18, 556-566, doi: https://doi.org/10.1016/j.cmet.2013.08.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rafty, L. A., Schmidt, M. T., Perraud, A. L., Scharenberg, A. M., and Denu, J. M. (2002) Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases, J. Biol. Chem., 277, 47114-47122, doi: https://doi.org/10.1074/jbc.M208997200.

    Article  CAS  PubMed  Google Scholar 

  78. Pickup, K. E., Pardow, F., Carbonell-Caballero, J., Lioutas, A., Villanueva-Canas, J. L., Wright, R. H. G., and Beato, M. (2019) Expression of oncogenic drivers in 3D cell culture depends on nuclear ATP synthesis by NUDT5, Cancers, 11, doi: https://doi.org/10.3390/cancers11091337.

    Article  Google Scholar 

  79. Perraud, A. L., Shen, B., Dunn, C. A., Rippe, K., Smith, M. K., Bessman, M. J., Stoddard, B. L., and Scharenberg, A. M. (2003) NUDT9, a member of the Nudix hydrolase family, is an evolutionarily conserved mitochondrial ADP-ribose pyrophosphatase, J. Biol. Chem., 278, 1794-1801, doi: https://doi.org/10.1074/jbc.M205601200.

    Article  CAS  PubMed  Google Scholar 

  80. Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B. J., Castronovo, V., Maechler, P., and Verdin, E. (2007) Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase, J. Biol. Chem., 282, 33583-33592, doi: https://doi.org/10.1074/jbc.M705488200.

    Article  CAS  PubMed  Google Scholar 

  81. 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., Wolberger, C., Prolla, T. A., Weindruch, R., Alt, F. W., and Guarente, L. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells, Cell, 126, 941-954, doi: https://doi.org/10.1016/j.cell.2006.06.057.

    Article  CAS  PubMed  Google Scholar 

  82. Zhang, J., Zhang, J., Benovic, J. L., Sugai, M., Wetzker, R., Gout, I., and Rittenhouse, S. E. (1995) Sequestration of a G-protein beta gamma subunit or ADP-ribosylation of Rho can inhibit thrombin-induced activation of platelet phosphoinositide 3-kinases, J. Biol. Chem., 270, 6589-6594, doi: https://doi.org/10.1074/jbc.270.12.6589.

    Article  CAS  PubMed  Google Scholar 

  83. Jacobson, E. L., Cervantes-Laurean, D., and Jacobson, M. K. (1997) ADP-ribose in glycation and glycoxidation reactions, Adv. Exp. Med. Biol., 419, 371-379, doi: https://doi.org/10.1007/978-1-4419-8632-0_49.

    Article  CAS  PubMed  Google Scholar 

  84. Perraud, A. L., Takanishi, C. L., Shen, B., Kang, S., Smith, M. K., Schmitz, C., Knowles, H. M., Ferraris, D., Li, W., Zhang, J., Stoddard, B. L., and Scharenberg, A. M. (2005) Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels, J. Biol. Chem., 280, 6138-6148, doi: https://doi.org/10.1074/jbc.M411446200.

    Article  CAS  PubMed  Google Scholar 

  85. Zharova, T. V., and Vinogradov, A. D. (1997) A competitive inhibition of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) by ADP-ribose, Biochim. Biophys. Acta, 1320, 256-264, doi: https://doi.org/10.1016/s0005-2728(97)00029-7.

    Article  CAS  PubMed  Google Scholar 

  86. Palazzo, L., Thomas, B., Jemth, A. S., Colby, T., Leidecker, O., Feijs, K. L., Zaja, R., Loseva, O., Puigvert, J. C., Matic, I., Helleday, T., and Ahel, I. (2015) Processing of protein ADP-ribosylation by Nudix hydrolases, Biochem. J., 468, 293-301, doi: https://doi.org/10.1042/BJ20141554.

    Article  CAS  PubMed  Google Scholar 

  87. Thirawatananond, P., McPherson, R. L., Malhi, J., Nathan, S., Lambrecht, M. J., Brichacek, M., Hergenrother, P. J., Leung, A. K. L., and Gabelli, S. B. (2019) Structural analyses of NudT16-ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins, Sci. Rep., 9, 5940, doi: https://doi.org/10.1038/s41598-019-39491-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang, F., Lou, L., Peng, B., Song, X., Reizes, O., Almasan, A., and Gong, Z. (2020) Nudix hydrolase NUDT16 regulates 53BP1 protein by reversing 53BP1 ADP-ribosylation, Cancer Res., 80, 999-1010, doi: https://doi.org/10.1158/0008-5472.CAN-19-2205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ward, I. M., Minn, K., van Deursen, J., and Chen, J. (2003) p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice, Mol. Cell. Biol., 23, 2556-2563, doi: https://doi.org/10.1128/mcb.23.7.2556-2563.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Belousova, E. A., Kutuzov, M. M., Ivankina, P. A., Ishchenko, A. A., and Lavrik, O. I. (2018) A new DNA break repair pathway involving PARP3 and base excision repair proteins, Dokl. Biochem. Biophys., 482, 233-237, doi: https://doi.org/10.1134/S1607672918050010.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Russian Science Foundation (project no. 18-74-00081) and Russian Foundation for Basic Research (project no. 19-34-60039).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. A. Kulikova.

Ethics declarations

The authors declare no conflict of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kulikova, V.A., Nikiforov, A.A. Role of NUDIX Hydrolases in NAD and ADP-Ribose Metabolism in Mammals. Biochemistry Moscow 85, 883–894 (2020). https://doi.org/10.1134/S0006297920080040

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297920080040

Keywords

Navigation