Analysis of the molecular mechanism of autophagosome formation from the viewpoint of lipid molecules

在自噬中，被称为自噬小体的新形成的双层膜结构隔离细胞质内容是最基本的过程。自噬小体的脂类组成在很大程度上仍不清楚，但从电子显微镜分析，人们推测自噬小体富含一些不寻常的脂类，如神经鞘脂脂。在这项研究中，我们发现神经鞘脂的合成是自噬正常进行所必需的。我们还认为肌醇磷酰神经酰胺参与了酵母中几种鞘磷脂之间的自噬。接下来，我们试图揭示神经鞘脂实际参与的过程。两个类似泛素的结合反应对于自噬是必不可少的。鞘磷脂对这些反应不是必需的。鞘磷脂的合成也不是构建PAS所必需的，PAS是一个空泡周围的结构，自噬相关的蛋白质在那里组装。抑制鞘磷脂合成不影响液泡水解酶的成熟。鞘磷脂被认为参与了自噬的其他过程。

In autophagy, sequestration of cytoplasmic contents by a newly formed double-membrane structure called the autophagosome is the most fundamental process. Lipid composition of the autophagosome is still largely unknown ; but form electron microscopic analyses, it has been speculated that the autophagosome is rich in some unusual lipids such as sphingolipids. In this study, we discovered that sphingolipid synthesis is required for proper progression of autophagy. We also suggested that inositolphosphoryl ceramide is involved in autophagy among several sphingolipid species in yeast. We next tried to reveal the process in which sphingolid is actually involved. Two ubiquitin-like conjugating reactions are essential for autophagy. Sphingolipid was not essential for these reactions. Sphingolipid synthesis was not required for the construction of the PAS a peri-vacuolar structure where autophagy-related proteins assemble, either. Maturation of vacuolar hydrolytic enzymes was not affected by inhibiting sphingolipid synthesis. Sphingolipid is considered to be involved in other processes in autophagy.