Ubiquitylation involved in Parkinson disease and membrane repair

2009 Fiscal Year Final Research Report

• Project/Area Number: 20770112
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: MATSUDA Noriyuki Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 主任研究員 (10332272)
• Project Period (FY): 2008 – 2009
• Keywords: ユビキチン / パーキンソン病 / Parkin / PINK1

Research Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Recent identification of genes linked to familial forms of PD, such as Parkin and PINK1, has revealed that ubiquitylation and mitochondrial integrity are key factors in disease pathogenesis. However, the exact mechanism underlying the functional interplay between Parkin-catalyzed ubiquitylation and PINK1-regulated mitochondrial quality control remains an enigma. We revealed the concrete mechanism underlying the functional interplay between ubiquitylation catalyzed by Parkin and mitochondrial quality control regulated by PINK1. These results provide crucial insight into the pathogenic mechanisms of PD. We also revealed that MG53 ubiquitin ligase is involved in plasma-membrane repair.

Research Products

• [Journal Article] Clement A Gautier, Yu-shin Sou, Shinji Saiki, Sumihiro Kawajiri, Fumiaki Sato, Mayumi Kimura, Masaaki Komatsu, Nobutaka Hattori and Keiji Tanaka (2010)
  • Author(s): Noriyuki Matsuda, Shigeto Sato, Kahori Shiba, Kei Okatsu, Keiko Saisho
  • Journal Title: PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. Journal of Cell Biology 189(2) Pages: 211-221
  • Peer Reviewed
• [Journal Article] MG53 nucleates assembly of cell membrane repair machinery. (2009)
  • Author(s): Chuanxi Cai, Haruko Masumiya, Noah Weisleder, Noriyuki Matsuda, Miyuki Nishi, Moonsun Hwang, Jae-Kyun Ko, Peihui Lin, Angela Thornton, Xiaoli Zhao, Zui Pan1, Shinji Komazaki, Marco Brotto, Hiroshi Takeshima, Jianjie Ma
  • Journal Title: Nat Cell Biol 11(1) Pages: 56-64
  • Peer Reviewed
• [Presentation] PINK1 recruits Parkin to damaged mitochondria for degradation. (2010)
  • Author(s): Noriyuki Matsuda
  • Organizer: The 2nd International Symposium of NCRC "Mitochondria and Autophagy in Neurodegenerative Diseases"
  • Place of Presentation: Kyung Hee University, Seoul, Korea (招待講演).
  • Year and Date: 2010-02-08
• [Presentation] パーキンソン病は, 膜電位を失ったミトコンドリアに対する品質管理不全病である (2009)
  • Author(s): 松田憲之, 佐藤栄人, 柴佳保里, 尾勝圭, 税所慶子, 曽友深, 斉木臣二, 河尻澄宏, 里史明, 木村まゆみ, 小松雅明, 服部信孝, 田中啓二
  • Organizer: 第32回日本分子生物学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20091209-20091212
• [Presentation] パーキンソン病は膜電位を失ったミトコンドリアのQuality control diseaseである (2009)
  • Author(s): 松田憲之, 田中啓二
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 20091021-20091024
• [Presentation] Parkin is retrieved from the cytoplasm to depolarized mitochondria, and triggers its degradation. (2009)
  • Author(s): Noriyuki Matsuda
  • Organizer: 5th International Symposium on Autophagy
  • Place of Presentation: Otsu, Shiga, Japan
  • Year and Date: 20090924-20090928
• [Remarks] 研究成果をホームページで公表
  • URL: http://www.rinshoken.or.jp/activities/t100419.html