title: Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset.
abstract: Circadian clocks are oscillatory systems that schedule daily rhythms of organismal behavior. The ability of the clock to reset its phase in response to external signals is critical for proper synchronization with the environment. In the model clock from cyanobacteria, the KaiABC proteins that comprise the core oscillator are directly sensitive to metabolites. Reduced ATP/ADP ratio and oxidized quinones cause clock phase shifts in vitro. However, it is unclear what determines the metabolic response of the cell to darkness and thus the magnitude of clock resetting. We show that the cyanobacterial circadian clock generates a rhythm in metabolism that causes cells to accumulate glycogen in anticipation of nightfall. Mutation of the histidine kinase CikA creates an insensitive clock-input phenotype by misregulating clock output genome wide, leading to overaccumulation of glycogen and subsequently high ATP in the dark. Conversely, we show that disruption of glycogen metabolism results in low ATP in the dark and makes the clock hypersensitive to dark pulses. The observed changes in cellular energy are sufficient to recapitulate phase-shifting phenotypes in an in vitro model of the clock. Our results show that clock-input phenotypes can arise from metabolic dysregulation and illustrate a framework for circadian biology where clock outputs feed back through metabolism to control input mechanisms.
authors.affiliation: Department of Molecular Genetics and Cell Biology, Institute for Genomics and Systems Biology, University of Chicago, 900 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Gopal K
authors.initials: GK
authors.lastname: Pattanayak
authors.affiliation: Department of Molecular Genetics and Cell Biology, Institute for Genomics and Systems Biology, University of Chicago, 900 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Phong
authors.affiliation: Department of Molecular Genetics and Cell Biology, Institute for Genomics and Systems Biology, University of Chicago, 900 East 57(th) Street, Chicago, IL 60637, USA. Electronic address: mrust@uchicago.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rust
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001683:Biological Clocks; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D046940:Synechococcus / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; D006003:Glycogen