Biological clocks allow organisms to anticipate cycles of feeding, activity, and rest so that metabolic enzymes in mitochondria are ready when needed. Peek et al. (see the Perspective by Rey and Reddy) describe a mechanism by which the biochemical elements of the circadian clock are linked to such control of mitochondrial metabolism. The clock controls rhythmic transcription of the gene encoding the rate-limiting enzyme required for synthesis of nicotinamide adenine dinucleotide (NAD+). The concentration of NAD+ in mitochondria determines the activity of the deacetylase SIRT3, which then controls acetylation and activity of key metabolic enzymes. NAD+ also influences clock function and thus appears to be a versatile point at which regulation of oxidative metabolism is coordinated with the daily cycles of energy consumption.
C. B. Peek, A. H. Affinati, K. M. Ramsey, H.-Y. Kuo, W. Yu, L. A. Sena, O. Ilkayeva, B. Marcheva, Y. Kobayashi, C. Omura, D. C. Levine, D. J. Bacsik, D. Gius, C. B. Newgard, E. Goetzman, N. S. Chandel, J. M. Denu, M. Mrksich, J. Bass, Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417 (2013). [Abstract] [Full Text]