Analysis of PINK1 stabilization molecular mechanism by Parkin

• Project/Area Number: 20790627
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: KAHORI Shiba Juntendo University, 大学院・医学研究科, 博士研究員 (30468582)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: parkin / PINK1 / Parkin / 家族性パーキンソン病

Research Abstract

In this study, we show that PINK1 recruits Parkin from the cytoplasm to mitochondria with low membrane potential to initiate the autophagic degradation of damaged mitochondria. Furthermore, we identified FK506-binding protein 38 : FKBP38 as a PINK1 binding protein with mitochondrial uncoupler Carbonyl cyanide m-chliirophenilhydrazone : CCCP treatment and FKBP38 stabilized PINK1 at the protein level.

Research Products

• [Journal Article] PINK1 stabilized by mitochondrial depokarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy (2010)
  • Author(s): Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K.
  • Journal Title: J Csll Biol 189(2) Pages: 211-21
  • Peer Reviewed
• [Journal Article] PINK1 recruits Parkin to damaged mitochondria for degradation. (2010)
  • Author(s): Matsuda N, Sato S, Shiba K, et al.
  • Journal Title: The Journal of cell biology (In press)
  • Peer Reviewed
• [Journal Article] Parkin stabilizes PINK1 through direct interaction (2009)
  • Author(s): Shiba K, Arai T, Sato S, Kubo S, Oba Y, Mizuno Y, Hattori N.
  • Journal Title: Biochem Biophys Res Commun 383(3) Pages: 331-5
  • Peer Reviewed
• [Journal Article] Parkn stabilizes PINK1 through direct interaction. (2009)
  • Author(s): Shiba K, Arai T, Sato S, et al.
  • Journal Title: Biochem Biophys Res Commun. 383(3) Pages: 331-5
  • Peer Reviewed
• [Journal Article] Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease
  • Author(s): Fukae J, Sato S, Shiba K, Sato K, Mori H, Sharp PA, Mizuno Y, Hattori N.
  • Journal Title: FEBS Lett. 583(3) Pages: 521-5
  • Peer Reviewed
• [Presentation] PINK1結合因子とPINK1安定化機構の関与 (2009)
  • Author(s): 柴佳保里、佐藤栄人、斉木臣二、服部信孝
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2009-05-21
• [Presentation] 家族性パーキンソン病原因遺伝子産物PINK1結合因子の解析 (2009)
  • Author(s): 柴佳保里
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台国際ヤンター
  • Year and Date: 2009-05-21
• [Presentation] ParkinによるPINK1安定化機構の解析 (2008)
  • Author(s): 柴佳保里
  • Organizer: 日本分子生物学年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09