Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.
Biochem Biophys Res Commun. 2011 Jul 15;410(4):786-91. doi: 10.1016/j.bbrc.2011.06.061. Epub 2011 Jun 14.
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.
在真核生物中，自噬是一种保守的蛋白质降解系统，通过用双层膜结构（称为自噬体）包围细胞质成分，并将它们递送至液泡/溶酶体的溶酶体隔间，从而降解细胞质成分。已知某些 Atg 蛋白参与自噬，但涉及的脂质分子的身份和功能在很大程度上仍不清楚。我们使用酿酒酵母研究了鞘脂在自噬中的作用。抑制最简单的复合鞘脂，即肌醇磷酸神经酰胺（IPC）的合成，导致自噬活性降低。使用鞘脂合成第一步的抑制剂，myriocin，也得到了类似的结果。我们的结果表明，鞘脂，特别是 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前自噬体结构（PAS）的形成没有影响。这些结果表明，鞘脂不参与导致 PAS 形成的细胞信号转导，但可能参与自噬体形成的过程。
