Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genesMore about Open Access at the Crick
Authors listGuillaume Rey Nikolay B Milev Utham K Valekunja Ratnasekhar Ch Sandipan Ray Mariana Silva Dos Santos Andras D Nagy Robin Antrobus James Macrae Akhilesh B Reddy
Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, S2 cells are regarded as "non-rhythmic" cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24-h cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24-h metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in and other eukaryotic systems.
Journal Molecular Systems Biology
Issue number 8