Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae
Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae
复制标题
鞘脂合成参与酿酒酵母的自噬
DOI：
10.1016/j.bbrc.2011.06.061
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kihara A
中科院分区：
文献类型：
--
作者：
Yamagata M;Obara K;Kihara A
在真核生物中，自噬是一种保守的蛋白质降解系统，通过用称为自噬体的双膜结构包围细胞质成分，并将其递送至液泡/溶酶体的裂解室，从而降解细胞质成分。已知某些 Atg 蛋白参与自噬，但所涉及的脂质分子的身份和功能仍然很大程度上未知。我们使用酿酒酵母研究了鞘脂在自噬中的参与。抑制最简单的复杂鞘脂——肌醇磷酸神经酰胺（IPC）的合成，会导致自噬活性降低。使用多球菌素（鞘脂合成第一步的抑制剂）获得了类似的结果。我们的结果表明鞘脂，尤其是 IPC，是自噬所必需的。鞘脂合成的抑制对 Atg12-Atg5 或 Atg8-磷脂酰乙醇胺缀合物的形成、液泡蛋白酶的成熟或自噬体前结构 (PAS) 的形成没有影响。这些结果表明鞘脂不参与导致 PAS 形成的细胞信号传导，但可能参与自噬体形成过程。
In eukaryotes, autophagy is a conserved protein degradation system that degrades cytoplasmic components by encompassing them with double-membrane structures, called autophagosomes, and delivering them to the lytic compartments of vacuoles/lysosomes. Certain Atg proteins are known to be involved in autophagy, yet the identity and function of lipid molecules involved remain largely unknown. We investigated the involvement of sphingolipids in autophagy using Saccharomyces cerevisiae. Inhibiting synthesis of the simplest complex sphingolipid, inositol phosphorylceramide (IPC), resulted in reduced autophagic activities. Similar results were obtained using myriocin, an inhibitor of the first step in sphingolipid synthesis. Our results indicate that sphingolipids, especially IPC, are required for autophagy. Inhibition of sphingolipid synthesis had no effect on formation of Atg12-Atg5 or Atg8-phosphatidylethanolamine conjugates, on maturation of vacuolar proteases, or on formation of the pre-autophagosomal structure (PAS). These results suggest that sphingolipids are not involved in the cellular signaling that leads to formation of the PAS, but may be involved in the process of autophagosome formation.