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

Ch, Ratnasekhar and Rey, Guillaume and Ray, Sandipan and et al, . (2021) Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells. Nature Communications, 12 (1). pp. 1-14. ISSN 2041-1723

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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. © 2021, The Author(s).

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IITH Creators:

IITH Creators	ORCiD
Ray, Sandipan	https://orcid.org/0000-0002-9960-5768

Item Type:

Article

Additional Information:

A.B.R. acknowledges funding from the Perelman School of Medicine, University of Pennsylvania, and the Institute for Translational Medicine and Therapeutics (ITMAT), Perelman School of Medicine, University of Pennsylvania. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number DP1DK126167 to A.B.R. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank J. Millar of the University of Pennsylvania Institute of Diabetes, Obesity and Metabolism (IDOM) Metabolic Tracing Core for carbon labeling experiments. A.B.R. also acknowledges funding from the European Research Council (ERC Starting Grant No. 281348, MetaCLOCK), the EMBO Young Investigators Programme, and the Lister Institute of Preventive Medicine. A.B.R. was supported in part by a Wellcome Trust Senior Fellowship in Clinical Science (100333/Z/12/Z) at the University of Cambridge, and also in part by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001534), the UK Medical Research Council (FC001534), and the Wellcome Trust (FC001534). G.R. was supported by an Advanced SNSF Postdoctoral Mobility Fellowship and an EMBO Long-Term Fellowship. We thank P. Grice for assistance with NMR experiments, and J. Jones for help with blood sampling for preliminary experiments. We are also grateful for access to the MRC Biomedical NMR Centre at the Francis Crick Institute.

Uncontrolled Keywords:

Animals; ARNTL Transcription Factors; 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

Subjects:

Others > Biotechnology

Divisions:

Department of Biotechnology

Depositing User:

. LibTrainee 2021

Date Deposited:

23 Sep 2022 04:51

Last Modified:

23 Sep 2022 04:51

URI:

http://raiithold.iith.ac.in/id/eprint/10665