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

在自噬过程中，被称为自噬体的新形成的双膜结构隔离细胞质内容物是最基本的过程。自噬体的脂质组成在很大程度上仍然是未知的；但通过电镜分析，人们推测自噬体富含一些不寻常的脂质，如鞘脂。在这项研究中，我们发现鞘脂的合成是自噬正常进行所必需的。我们还认为肌磷酰神经酰胺参与了酵母中几种鞘脂类的自噬。接下来，我们试图揭示鞘脂实际上参与的过程。两个泛素样结合反应是自噬所必需的。鞘脂不是这些反应所必需的。鞘脂合成也不需要PAS的构建，PAS是自噬相关蛋白聚集的空泡周围结构。抑制鞘脂合成不影响液泡水解酶的成熟。鞘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.