ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism

Inositol phosphates (IPs) are a class of signaling molecules regulating cell physiology. The best-characterized IP, the calcium release factor IP3, is generated by phospholipase C hydrolysis of phosphoinositides lipids. For historical and technical reasons, IPs synthesis is believed to originate from the lipid-generated IP3. While this is true in yeast, our work has demonstrated that other organisms use a “soluble” (nonlipid) route to synthesize IPs. This soluble pathway depends on the metabolic status of the cells, and is under the control of the kinase ITPK1, which phosphorylates inositol monophosphate likely generated from glucose. The data shed light on the evolutionary origin of IPs, signaling and tightening the link between these small molecules and basic metabolism