Abstract 1651 Enhanced transport of glycerophosphocholine, a common lipid metabolite, inhibits growth of Saccharomyces cerevisiae and Schizosaccharomyces pombe

Glycerophosphocholine (GPC) is a ubiquitous product of phosphatidylcholine (PC) turnover found in most eukaryotic cells. GPC and other glycerophosphodiesters, such as glycerophosphoinositol (GPI), can also be transported into the cell via the Git-type transporters. These transporters are upregulated upon phosphate starvation and repressed under phosphate-replete conditions in both S. cerevisiae and S. pombe. Intracellular GPC has two immediate metabolic routes; GPC can be reacylated by the acyltransferase encoded by Gpc1 or catabolized by the glycerophosphodiesterase Gde1 to produce glycerol-3-phosphate (G3P) and choline. Here, we report that unrestrained transport of GPC leads to growth inhibition in both organisms. We demonstrate that the toxicity associated with enhanced GPC uptake requires Gde1 in S. cerevisiae. In S. pombe, enhanced GPC transport results in growth inhibition when Gde1 is intact and inositol pyrophosphates (IPPs) are available in high levels. In S. pombe, both the catalytic (GPDE) and SPX (inositol pyrophosphate binding) domains of Gde1 are required for mediating cellular toxicity. Experiments examining the role of the SPX domain in regulating the catalytic activity of Gde1 are underway. Enhanced GPC uptake leads to a small but significant increase in cell death as monitored by propidium iodide staining. Experiments probing the mechanism of GPC toxicity are ongoing. Overall, our findings suggest an intriguing novel role for GPC, a common lipid metabolite, in modulating cell proliferation. The Patton-Vogt lab acknowledges NIH grant R15GM104876.