Elucidation of the molecular mechanims of Parkin-PINK1 triggered mitophagy by using budding yeast

利用芽殖酵母阐明 Parkin-PINK1 触发线粒体自噬的分子机制

• 批准号: 24657072
• 负责人: ENDO Toshiya
• 金额: $ 2.66万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24657072/
• 关键词: 酵母; ミトコンドリア; パーキンソン病; PINK1; Parkin

In eukaryotic cells, aberrant mitochondria are selectively removed by a process called mitophagy, and PINK1 and Parkin, causative gene products for Parkinsonism, mediate this process in mammalian cells while yeast cells lack the Parkin-PINK1 system. Here we expressed Parkin and a PINK1 fusion protein that is artificially targeted to the mitochondrial outer membrane in yeast cells. Parkin expressed in the cytosol was recruited to the mitochondrial outer membrane by PINK1 in a manner that depends on the kinase activity of PINK1. The recruited Parkin was further phosphorylated and ubiquitinated like the case for mammalian cells. The yeast cells with artificially expressed Pakin-PINK1 can thus offer a useful tool to analyze the functions of the Parkin-PINK1 system.

在真核细胞中，异常的线粒体通过一种称为线粒体自噬的过程被选择性地去除，而PINK 1和Parkin，帕金森症的致病基因产物，在哺乳动物细胞中介导了这一过程，而酵母细胞缺乏Parkin-PINK 1系统。 在这里，我们表达了帕金和PINK 1融合蛋白，该蛋白被人工靶向酵母细胞中的线粒体外膜。 在细胞质中表达的Parkin被PINK 1以依赖于PINK 1的激酶活性的方式募集到线粒体外膜。 被招募的帕金进一步被磷酸化和泛素化，就像哺乳动物细胞的情况一样。 因此，人工表达Pakin-PINK 1的酵母细胞可以为分析Parkin-PINK 1系统的功能提供有用的工具。

项目成果

How to make mitochondria from proteins and lipids in the cell?

如何利用细胞中的蛋白质和脂质制造线粒体？

• 发表时间: 2013
• 作者: Koyano;F.;Okatsu;K.;Kosako;H.;Tamura;Y.;Go;E.;Kimura;M.;Kimura;Y.;Tsuchiya;H.;Yoshihara;H.;Hirokawa;T.;Endo;T.;Fon. E. A.;Trempe;J. F.;Saeki;Y.;Tanaka;K.;and Matsuda;N.;遠藤斗志也;Toshiya Endo
• 通讯作者: Toshiya Endo

OM45 is imported into the mitochondrial intermembrane space via a novel import pathway

OM45 通过一种新的导入途径导入线粒体膜间隙

• 发表时间: 2013
• 作者: Jiyao Song;Tohru Yoshihisa;Yasushi Tamura;and Toshiya Endo
• 通讯作者: and Toshiya Endo

How the cell makes mitochondria: from the viewpoints of transport of proteins and lipids

细胞如何制造线粒体：从蛋白质和脂质运输的角度来看

• 发表时间: 2013
• 作者: Jiyao Song;Tohru Yoshihissa;Yasushi Tamura;Toshiya Endo;Toshiya Endo;Toshiya Endo;Toshiya Endo
• 通讯作者: Toshiya Endo

New insight into mitochondrial biogenesis Organelle Homeostasis Research Center : Kick-off Symposium

线粒体生物发生的新见解细胞器稳态研究中心：启动研讨会

• 发表时间: 2013
• 作者: Jiyao Song;Tohru Yoshihisa;Yasushi Tamura;and Toshiya Endo;Toshiya Endo;Toshiya Endo
• 通讯作者: Toshiya Endo

Transport, assembly, and quality control of mitochondrial proteins in yeast

酵母中线粒体蛋白的运输、组装和质量控制

• 发表时间: 2013
• 作者: Jiyao Song;Tohry Yoshihisa;Yasushi Tamura;and Toshiya Endo;Toshiya Endo
• 通讯作者: Toshiya Endo