Homologs of Ancestral CNNM Proteins Affect Magnesium Homeostasis and Circadian Rhythmicity in a Model Eukaryotic Cell

Biological rhythms are ubiquitous across organisms and coordinate key cellular processes. Oscillations of Mg levels in cells are now well-established, and due to the critical roles of Mg in cell metabolism, they are potentially fundamental for the circadian control of cellular activity. The identity of the transport proteins responsible for sustaining Mg levels in eukaryotic cells remains hotly debated, and several are restricted to specific groups of higher eukaryotes. Here, using the eukaryotic minimal model cells of , we report two homologs of common descents of the Cyclin M (CNNM)/CorC protein family. Overexpression of these proteins leads to a reduction in the overall magnesium content of cells and a lengthening of the period of circadian gene expression rhythms. However, we observed a paradoxical increase in the magnesium content of the organelle fraction. The chemical inhibition of Mg transport has a synergistic effect on circadian period lengthening upon the overexpression of one CNNM homolog, but not the other. Finally, both homologs rescue the deleterious effect of low extracellular magnesium on cell proliferation rates. Overall, we identified two CNNM proteins that directly affect Mg homeostasis and cellular rhythms.