Unperverted synthesis of complex sphingolipids is essential for cell survival under nitrogen starvation
Unperverted synthesis of complex sphingolipids is essential for cell survival under nitrogen starvation
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DOI：
10.1111/gtc.12062
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发表时间：
2013-08
期刊：
影响因子：
2.1
通讯作者：
M. Yamagata;K. Obara;A. Kihara
中科院分区：
文献类型：
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作者：
M. Yamagata;K. Obara;A. Kihara
膜动力学的变化是已知的发生在细胞面临饥饿。然而，生物膜的主要脂质成分鞘脂在饥饿反应期间的功能仍不清楚。在这项研究中，我们发现，酵母细胞缺乏编码甘露糖肌醇磷酸神经酰胺（MIPC）酶（csg 1 Δ csh 1 Δ）的基因发生迅速的细胞死亡时，氮饥饿，但不是在碳饥饿或碳和氮饥饿。NaN 3的加入阻止了氮饥饿诱导的csg 1 Δ csh 1 Δ细胞的细胞死亡，表明这种快速细胞死亡需要能量产生。细胞死亡是由含有植物鞘氨醇的肌醇磷酸神经酰胺（IPC）物质的积累引起的。通过用钙螯合剂处理细胞或通过在氮饥饿之前将培养基改变为无Ca 2+培养基来去除Ca 2+，拯救细胞免于死亡。大约一半的细胞死亡后不久，空泡崩溃，而在另一半，细胞质中的形态变化之前空泡破裂。由于液泡是主要的Ca ~（2+）储存细胞器，我们认为液泡直接或间接地参与了细胞死亡。我们在这里报告，复杂鞘脂的正常合成对于细胞在氮饥饿培养基中的存活是重要的。
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 Ca2+ by treating the cells with a calcium chelator or by changing the medium to a Ca2+‐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 Ca2+ 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.