Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells
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Ratnasekhar Ch Guillaume Rey Sandipan Ray Pawan K Jha Paul Driscoll Mariana Silva Dos Santos Dania M Malik Radoslaw Lach Aalim M Weljie James Macrae Utham K Valekunja Akhilesh B ReddyAbstract
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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Journal Nature Communications
Volume 12
Issue number 1
Pages 377
Available online
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Publisher website (DOI) 10.1038/s41467-020-20479-4
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Europe PubMed Central 33452240
Pubmed 33452240
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