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Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells.

Published version
Peer-reviewed

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Authors

Ray, Sandipan 
Jha, Pawan K 

Abstract

Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

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Keywords

ARNTL Transcription Factors, Animals, Cells, Cultured, Circadian Clocks, Circadian Rhythm, Erythrocytes, Fibroblasts, Gene Knockout Techniques, Glycolysis, Healthy Volunteers, Humans, Male, Metabolomics, Mice, Oxidation-Reduction, Pentose Phosphate Pathway, Primary Cell Culture

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

12

Publisher

Springer Science and Business Media LLC