Unperverted synthesis of complex sphingolipids is essential for cell survival under nitrogen starvation

Changes in membrane dynamics are known to occur in cells faced with starvation. However, the functions of the major lipid components of biological membranes, sphingolipids, during the starvation response remain unclear. In this study, we found that yeast cells lacking genes encoding mannosylinositol phosphorylceramide (MIPC) synthases (csg1Δ csh1Δ) underwent rapid cell death upon nitrogen starvation, but not upon carbon starvation or carbon and nitrogen starvation. Addition of NaN3 prevented the nitrogen starvation-induced cell death of the csg1Δ csh1Δ cells, indicating that energy production is required for this rapid cell death. The cell death was caused by an accumulation of inositol phosphorylceramide (IPC) species containing phytosphingosine. Removing Ca(2+) by treating the cells with a calcium chelator or by changing the medium to a Ca(2+) -free medium before nitrogen starvation rescued the cells from death. Approximately half of the cells died shortly after collapse of the vacuole, whereas in the other half, morphological changes in the cytoplasm preceded vacuole disruption. Because the vacuole is the major Ca(2+) storage organelle, we suggest that the vacuole is involved in the cell death either directly or indirectly. We report here that normal synthesis of complex sphingolipids is important for cell survival in nitrogen-starved medium.