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

从脂质分子角度分析自噬体形成的分子机制

• 批准号: 21770129
• 负责人: OBARA Keisuke
• 金额: $ 2.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21770129/
• 关键词: 脂質; タンパク質; オートファジー; タンパク質分解; スフィンゴ; スフィンゴ脂質; オートファゴソーム; 脂肪酸; 酵母; 液胞

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.

在自噬中，通过新形成的双膜结构（称为自噬体的新形成的双膜结构）对细胞质含量的固结是最基本的过程。自噬体的脂质成分在很大程度上是未知的。但是形成电子显微镜分析，已经推测自噬体富含一些异常的脂质，例如鞘脂。在这项研究中，我们发现鞘脂合成是自噬的正确进展所必需的。我们还建议，酵母中几种鞘脂物种中的二酚磷酸化神经酰胺参与了自噬。接下来，我们试图揭示鞘脂实际涉及的过程。两个类似泛素的共轭反应对于自噬至关重要。鞘脂对于这些反应并不是必需的。在pA构建PAS的螺旋脂合成的情况下，与自噬相关蛋白组装的PAS结构也不需要。液泡水解酶的成熟不受抑制鞘脂合成的影响。鞘脂被认为与自噬的其他过程有关。

项目成果

PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast.

• DOI: 10.1155/2011/498768
• 发表时间: 2011
• 期刊: Journal of lipids
• 影响因子: 5.3
• 作者: Obara K;Ohsumi Y
• 通讯作者: Ohsumi Y

酵母を用いたオートファジー誘導におけるスフィンゴ脂質の機能解析

使用酵母诱导自噬诱导鞘脂的功能分析

• 发表时间: 2009
• 作者: 山形麻旗;小原圭介;木原章雄
• 通讯作者: 木原章雄

窒素飢餓応答におけるスフィンゴ脂質の役割

鞘脂在氮饥饿反应中的作用

• 发表时间: 2010
• 作者: 山形麻旗;小原圭介;木原章雄
• 通讯作者: 木原章雄