Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online March 12, 2009
Science DOI: 10.1126/science.1170803

Reports

Submitted on January 12, 2009
Accepted on March 2, 2009

Circadian Control of the NAD+ Salvage Pathway by CLOCK-SIRT1

Yasukazu Nakahata 1, Saurabh Sahar 1, Giuseppe Astarita 1, Milota Kaluzova 1, Paolo Sassone-Corsi 1*

1 Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA.

* To whom correspondence should be addressed.
Paolo Sassone-Corsi , E-mail: psc{at}uci.edu

Many metabolic and physiological processes display circadian oscillations. We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the NAD+-dependent histone deacetylase SIRT1. Here, we show that intracellular NAD+ levels cycle with a 24-hour rhythm, an oscillation driven by the circadian clock. CLOCK:BMAL1 regulate the circadian expression of NAMPT (nicotinamide phosphoribosyltransferase), a rate limiting step enzyme in the NAD+ salvage pathway. SIRT1 is recruited to the Nampt promoter and contributes to the circadian synthesis of its own coenzyme. Using the specific inhibitor FK866, we demonstrate that NAMPT is required to modulate circadian gene expression. Our findings reveal an interlocked transcriptional-enzymatic feedback loop that governs the molecular interplay between cellular metabolism and circadian rhythms.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular control of circadian metabolic rhythms.
S. Li and J. D. Lin (2009)
J Appl Physiol 107, 1959-1964
   Abstract »    Full Text »    PDF »
How nuclear receptors tell time.
M. Teboul, A. Grechez-Cassiau, F. Guillaumond, and F. Delaunay (2009)
J Appl Physiol 107, 1965-1971
   Abstract »    Full Text »    PDF »
Rev-erb-{alpha}: an integrator of circadian rhythms and metabolism.
H. Duez and B. Staels (2009)
J Appl Physiol 107, 1972-1980
   Abstract »    Full Text »    PDF »
Clock genes and metabolic disease.
B. Marcheva, K. M. Ramsey, A. Affinati, and J. Bass (2009)
J Appl Physiol 107, 1638-1646
   Abstract »    Full Text »    PDF »
Working around the clock: circadian rhythms and skeletal muscle.
X. Zhang, T. J. Dube, and K. A. Esser (2009)
J Appl Physiol 107, 1647-1654
   Abstract »    Full Text »    PDF »
Response to Comment on "The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop".
A. N. Dodd, M. J. Gardner, C. T. Hotta, K. E. Hubbard, N. Dalchau, F. C. Robertson, J. Love, D. Sanders, and A. A. R. Webb (2009)
Science 326, 230
   Abstract »    Full Text »    PDF »
Anticipating anticipation: pursuing identification of cardiomyocyte circadian clock function.
M. E. Young (2009)
J Appl Physiol 107, 1339-1347
   Abstract »    Full Text »    PDF »
SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms.
B. Jung-Hynes and N. Ahmad (2009)
FASEB J 23, 2803-2809
   Abstract »    Full Text »    PDF »
Calorie restriction and the exercise of chromatin.
A. Vaquero and D. Reinberg (2009)
Genes & Dev. 23, 1849-1869
   Abstract »    Full Text »    PDF »
Enzymes in the NAD+ Salvage Pathway Regulate SIRT1 Activity at Target Gene Promoters.
T. Zhang, J. G. Berrocal, K. M. Frizzell, M. J. Gamble, M. E. DuMond, R. Krishnakumar, T. Yang, A. A. Sauve, and W. L. Kraus (2009)
J. Biol. Chem. 284, 20408-20417
   Abstract »    Full Text »    PDF »
A Circadian Loop asSIRTs Itself.
H. Wijnen (2009)
Science 324, 598-599
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)