Intracellular potassium levels orchestrate circadian rhythmicity and cell division

Abstract

Abstract Circadian (~24 h) rhythms are a fundamental feature of life, and their disruption increases the risk of infectious diseases, metabolic disorders, and cancer. We previously identified circadian oscillations in intracellular potassium concentrations in cells across kingdoms. Using highly divergent eukaryotic cell types, we now show that potassium levels act to regulate the period and phase of clock gene expression rhythms, therefore establishing intracellular potassium as a bona fide regulator of cellular circadian rhythms. Intracellular potassium also regulates critical events in the cell cycle. Strikingly, we observe that manipulating potassium levels inhibits cell proliferation in a circadian phase-dependent manner. As the timing of cell division is tuned by the circadian clock, we hypothesised that potassium rhythms could mechanistically link cell proliferation rhythms to the circadian cycle. In line with this hypothesis, we find that potassium levels are not only sufficient to instruct the timing of cell proliferation, but also essential to maintain coherent coupling between circadian rhythms and proliferation rhythms. These results establish circadian potassium rhythms as a primary factor coupling the cell- and circadian cycles in eukaryotic cells.