Sirtuins and the circadian clock: bridging chromatin and metabolism.

The circadian clock is a finely tuned system of transcriptional and translational regulation that is required for daily synchrony of organismal physiological processes. Additional layers of complexity that contribute to efficient clock function involve posttranslational modifications and enzymatic feedback loops. SIRT1, the founding member of the sirtuin family of protein deacetylases, was the first sirtuin to be reported to modulate circadian function. SIRT1 affects the circadian clock by its actions in the nucleus. Moreover, recent data implicate SIRT3 and SIRT6 in controlling mitochondrial and nuclear circadian functions, revealing previously unappreciated roles that extend to various subcellular domains, including fatty acid metabolism in the mitochondria. This review focuses on the roles of sirtuins in directing circadian functions in diverse organelles and speculates on the endogenous signals that may mediate the segregated roles of this family of enzymes.