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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Ch R,Rey G,Ray S,Jha PK,Driscoll PC,Dos Santos MS,Malik DM,Lach R,Weljie AM,MacRae JI,Valekunja UK,Reddy ABdoi
10.1038/s41467-020-20479-4subject
Has Abstractpub_date
2021-01-15 00:00:00pages
377issue
1issn
2041-1723pii
10.1038/s41467-020-20479-4journal_volume
12pub_type
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