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

• Project/Area Number: 24657072
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Nagoya University
• Principal Investigator: ENDO Toshiya 名古屋大学, 理学(系)研究科(研究院), 教授 (70152014)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 酵母 / ミトコンドリア / パーキンソン病 / PINK1 / Parkin

Research Abstract

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.

Research Products

• [Journal Article] A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex (2014)
  • Author(s): Song J, Tamura Y, Yoshihisa T, Endo T
  • Journal Title: EMBO Rep. Volume: (in press) Pages: 670-677
  • DOI: 10.1002/embr.201338142
  • Peer Reviewed / Open Access
• [Journal Article] Ubiquitin is phosphorylated by PINK1 to activate parkin. (2014)
  • Author(s): 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.
  • Journal Title: Nature Volume: 510(in press) Issue: 7503 Pages: 162-166
  • DOI: 10.1038/nature13392
  • Peer Reviewed
• [Presentation] タンパク質と脂質の輸送と合成からみた酵母ミトコンドリアの生合成機構 (2013)
  • Author(s): 遠藤斗志也
  • Organizer: 第185回酵母細胞研究会例会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-22
  • Invited
• [Presentation] How to make mitochondria from proteins and lipids in the cell? (2013)
  • Author(s): Toshiya Endo
  • Organizer: CEF(Cluster of Excellence Frankfurt)/BMLS (Buchmann Institute of Molecular Life Sciences) Lecture at the Goethe University Frankfurt
  • Place of Presentation: Frankfurt, Germany
  • Year and Date: 2013-08-29
  • Invited
• [Presentation] OM45 is imported into the mitochondrial intermembrane space via a novel import pathway (2013)
  • Author(s): Jiyao Song, Tohru Yoshihisa, Yasushi Tamura, and Toshiya Endo
  • Organizer: 第77回日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] Organelle homeostasis research in Japan (2013)
  • Author(s): Toshiya Endo
  • Organizer: Organelle Homeostasis Research Center : Workshop on Homeostasis Research
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-23
  • Invited
• [Presentation] New insight into mitochondrial biogenesis Organelle Homeostasis Research Center : Kick-off Symposium (2013)
  • Author(s): Toshiya Endo
  • Organizer: EMBO Conference : From Structure to Function of Translocation Machines
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-22
  • Invited
• [Presentation] How the cell makes mitochondria : from the viewpoints of transport of proteins and lipids (2013)
  • Author(s): Toshiya Endo
  • Organizer: DynaMito 2013 : The 4th International Symposium on Dynamics of Mitochondria - from Molecular Mechanisms to Physiological Functions and Disease
  • Place of Presentation: 沖縄
  • Invited
• [Presentation] Novel pathway for import of yeast OM45 into the mitochondrial intermembrane space (2013)
  • Author(s): Jiyao Song, Tohry Yoshihisa, Yasushi Tamura, and Toshiya Endo
  • Organizer: DynaMito 2013 : The 4th International Symposium on Dynamics of Mitochondria - from Molecular Mechanisms to Physiological Functions and Disease 2013
  • Place of Presentation: 沖縄
• [Presentation] Transport, assembly, and quality control of mitochondrial proteins in yeast (2013)
  • Author(s): Toshiya Endo
  • Organizer: The 26th International Conference on Yeast Genetics and Molecular Biology
  • Place of Presentation: Frankfurt, Germany
• [Presentation] OM45 is imported into the mitochondrial intermembrane space via a novel import pathway (2013)
  • Author(s): Jiyao Song, Tohru Yoshihissa, Yasushi Tamura, Toshiya Endo
  • Organizer: 第65回細胞生物学会大会
  • Place of Presentation: 名古屋
• [Presentation] New perspective on biogenesis of mitochondrial proteins and lipids (2013)
  • Author(s): Toshiya Endo
  • Place of Presentation: Dubrovnik, Croatia
  • Invited
• [Presentation] Transport, assembly, and quality control of mitochondrial proteins in yeast (2013)
  • Author(s): Toshiya Endo
  • Organizer: Yeast 2013 (The 26th International Conference on Yeast Genetics and Molecular Biology)
  • Place of Presentation: Frankfurt, Germany
  • Invited
• [Presentation] How the cell makes mitochondria: from the viewpoints of transport of proteins and lipids (2013)
  • Author(s): Toshiya Endo
  • Organizer: DynaMito 2013: The 4th International Symposium on Dynamics of Mitochondria - from Molecular Mechanisms to Physiological Functions and Disease
  • Place of Presentation: 沖縄
  • Invited
• [Presentation] New perspective on biogenesis of mitochondrial proteins and lipids (2012)
  • Author(s): Toshiya Endo
  • Organizer: 第85回日本生化学会大会シンポジウム「New Paradigm of Organelle Biology and Physiology」
  • Place of Presentation: 福岡
  • Invited
• [Presentation] New perspective on import and maintenance of mitochondrial proteins (2012)
  • Author(s): Toshiya Endo
  • Organizer: SFB594 3rd International Symposium Molecular Machines in Protein Folding and Translocation
  • Place of Presentation: Munich, Germany
  • Invited
• [Presentation] New perspective on import and maintenance of mitochondrial proteins (2012)
  • Author(s): Toshiya Endo
  • Organizer: SFB594 3rd International Symposium Molecular Machines in Protein Folding and Translocation
  • Place of Presentation: Munich, Germany
  • Invited
• [Presentation] New insight into mitochondrial biogenesis
  • Author(s): Toshiya Endo
  • Organizer: Organelle Homeostasis Research Center: Kick-off Symposium
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Organelle homeostasis research in Japan
  • Author(s): Toshiya Endo
  • Organizer: Organelle Homeostasis Research Center: Workshop on Homeostasis Research
  • Place of Presentation: 福岡
  • Invited
• [Remarks] 名古屋大学大学院理学研究科 物質理学専攻 生物化学研究室
  • URL: http://biochem.chem.nagoya-u.ac.jp/index.html