Calcium signaling is a universal carbon source signal transducer and effects an ionic memory of past carbon sources

Glucose is the preferred carbon source for most cells. However, cells may encounter other carbon sources that can be utilized. How cells match their metabolic gene expression to their carbon source, beyond a general glucose repressive system (catabolite repression), remains little understood. By studying the effect of up to seven different carbon sources on Snf1 phosphorylation and on the expression of downstream regulated genes, we searched for the mechanism that identifies carbon sources. We found that the glycolysis metabolites glucose-6-phosphate (G6P) and glucose-1-phosphate (G1P) play a central role in the adaptation of gene expression to different carbon sources. The ratio of G1P and G6P activates an analogue calcium signaling via the proton-exporter Pma1, to regulate downstream genes. The signaling pathway bifurcates with calcineurin reducingADH2(alcohol dehydrogenase) expression and with Cmk1 increasingZWF1(glucose-6-phosphate dehydrogenase) expression. Furthermore, calcium signaling is not only regulated by the present carbon source; it is also regulated by past carbon sources. We were able to manipulate thisionic memorymechanism to obtain high expression ofZWF1in media containing galactose. Our findings provide auniversalmechanism by which cells respond to all carbon sources.