Emerging Roles of NAD+ and Its Metabolites in Cell Signaling

Sci. Signal., 10 February 2009
Vol. 2, Issue 57, p. mr1
DOI: 10.1126/scisignal.257mr1

Emerging Roles of NAD+ and Its Metabolites in Cell Signaling

  1. Friedrich Koch-Nolte1,*,
  2. Friedrich Haag1,
  3. Andreas H. Guse2,
  4. Frances Lund3, and
  5. Mathias Ziegler4
  1. 1Institute of Immunology, Diagnostic Department, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
  2. 2The Calcium Signaling Group, Institute of Biochemistry and Molecular Biology I, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
  3. 3Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, 601 Elmwood Drive, Rochester, NY 14642, USA.
  4. 4Department of Molecular Biology, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
  1. *Corresponding author. E-mail, nolte{at}uke.de
A report on the NAD2008 symposium, Hamburg, Germany, 14 to 17 September 2008.


Nicotinamide adenine dinucleotide (NAD+) is the universal currency of energy metabolism and electron transfer. Recent studies indicate that apart from its role as a coenzyme, NAD+ and its metabolites also function in cell signaling pathways; for example, they are substrates for nucleotide-metabolizing enzymes and ligands for extra- and intracellular receptors and ion channels. Moreover, the NAD+ and NAD+ phosphate metabolites adenosine 5′-diphosphoribose (ADP-ribose), cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate (NAADP) have emerged as key second messengers in Ca2+ signaling. A symposium in Hamburg, Germany, brought together 120 researchers from various fields, who were all engaged in the molecular characterization of the key players of NAD+ signaling (www.NAD2008.de).


F. Koch-Nolte, F. Haag, A. H. Guse, F. Lund, and M. Ziegler, Emerging Roles of NAD+ and Its Metabolites in Cell Signaling. Sci. Signal. 2, mr1 (2009).

Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts
R. Felici, A. Lapucci, L. Cavone, S. Pratesi, R. Berlinguer-Palmini, and A. Chiarugi
Mol. Pharmacol. 87, 965-971 (1 June 2015)

Ruling out pyridine dinucleotides as true TRPM2 channel activators reveals novel direct agonist ADP-ribose-2'-phosphate
B. Toth, I. Iordanov, and L. Csanady
JGP 145, 419-430 (1 May 2015)

CD73 Protein as a Source of Extracellular Precursors for Sustained NAD+ Biosynthesis in FK866-treated Tumor Cells
A. Grozio, G. Sociali, L. Sturla, I. Caffa, D. Soncini, A. Salis, N. Raffaelli, A. De Flora, A. Nencioni, S. Bruzzone et al.
J Biol Chem 288, 25938-25949 (6 September 2013)

Pyridine Nucleotide Regulation of Cardiac Intermediary Metabolism
J. R. Ussher, J. S. Jaswal, and G. D. Lopaschuk
Circ. Res. 111, 628-641 (17 August 2012)

ASPARTATE OXIDASE Plays an Important Role in Arabidopsis Stomatal Immunity
A. P. Macho, F. Boutrot, J. P. Rathjen, and C. Zipfel
Plant Physiol. 159, 1845-1856 (1 August 2012)

Pharmacological Effects of Exogenous NAD on Mitochondrial Bioenergetics, DNA Repair, and Apoptosis
M. Pittelli, R. Felici, V. Pitozzi, L. Giovannelli, E. Bigagli, F. Cialdai, G. Romano, F. Moroni, and A. Chiarugi
Mol. Pharmacol. 80, 1136-1146 (1 December 2011)

Reciprocal Potentiation of the Antitumoral Activities of FK866, an Inhibitor of Nicotinamide Phosphoribosyltransferase, and Etoposide or Cisplatin in Neuroblastoma Cells
C. Travelli, V. Drago, E. Maldi, N. Kaludercic, U. Galli, R. Boldorini, F. Di Lisa, G. C. Tron, P. L. Canonico, A. A. Genazzani et al.
J. Pharmacol. Exp. Ther. 338, 829-840 (1 September 2011)

Nicotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus
J. Chang, B. Zhang, H. Heath, N. Galjart, X. Wang, and J. Milbrandt
Proc. Natl. Acad. Sci. USA 107, 21836-21841 (14 December 2010)

M. Pittelli, L. Formentini, G. Faraco, A. Lapucci, E. Rapizzi, F. Cialdai, G. Romano, G. Moneti, F. Moroni, A. Chiarugi et al.
J Biol Chem 285, 34106-34114 (29 October 2010)

Identification of Direct and Indirect Effectors of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel
B. Toth, and L. Csanady
J Biol Chem 285, 30091-30102 (24 September 2010)

Diadenosine Homodinucleotide Products of ADP-ribosyl Cyclases Behave as Modulators of the Purinergic Receptor P2X7
S. Bruzzone, G. Basile, M. P. Chothi, L. Nobbio, C. Usai, E. Jacchetti, A. Schenone, A. H. Guse, F. Di Virgilio, A. De Flora et al.
J Biol Chem 285, 21165-21174 (2 July 2010)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882