Effects of mitophagy on cell death in Parkinson's disease model cells

• Project/Area Number: 21790853
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: SAIKI Shinji Juntendo University, 医学部, 助手 (00339996)
• Co-Investigator(Renkei-kenkyūsha): HATTORI Nobutaka 順天堂大学, 医学部, 教授 (80218510) ; SATO Shigeto 順天堂大学, 医学部, 准教授 (00445537) ; HATANO Taku 順天堂大学, 医学部, 助教 (60338390) ; EGUCHI Hiroto 順天堂大学, 医学部, 助教 (20380868) ; IMOTO Masaya 慶應義塾大学, 理工学部, 教授 (60213253) ; TANIDA Isei 国立感染症研究所, 主任研究員 (30296868) ; MATSUDA Noriyuki 東京都臨床医学総合研究所, 研究員 (10332272) ; KOMATSU Masaaki 東京都臨床医学総合研究所, 参事研究員 (90356254) ; TANAKA Keiji 東京都臨床医学総合研究所, 所長代行 (10108871) ; AMO Taku 防衛大学, 校応用化学群, 助教 (40453922)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オートファジー / パーキンソン病 / ミトファジー

Research Abstract

PINK1/parkin-mediated mitophagy is attenuated by loss of each gene expression and pathogenic mutations of the genes and is triggered by PINK1 accumulation on the mitochondrial outer membrane. In PINK1-/- mouse embryonic fibroblasts, mitochondrial function is insufficient, whilst production of the reactive oxygen species is unchanged.
Caffeine, a well-known chemical with PD-onset retardation effects, induces apoptosis via enhancement of autophagy. Zonisamide prevents cell death via suppression of apoptotic pathway and induction of MnSOD expression.

Research Products

• [Journal Article] Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. (2011)
  • Author(s): Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Kei-Ichi Ishikawa, Sato S, Imoto M, Hattori N.
  • Journal Title: Autophagy 7 Pages: 176-87
  • Peer Reviewed
• [Journal Article] Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. (2011)
  • Author(s): Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA, Shen J, Ohta S, Hattori N.
  • Journal Title: Neurobiol Dis 41 Pages: 111-118
  • Peer Reviewed
• [Journal Article] Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. (2011)
  • Author(s): Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Kei-Ichi Ishikawa, Sato S, Imoto M, Hattori N.
  • Journal Title: Autophagy Volume: 7 Pages: 176-187
  • Peer Reviewed
• [Journal Article] Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. (2011)
  • Author(s): Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA, Shen J, Ohta S, Hattori N.
  • Journal Title: Neurobiology of Diseases Volume: 41 Pages: 111-118
  • Peer Reviewed
• [Journal Article] Zonisamide reduces cell death in SH-SY5Y cells via an anti-apoptotic effect and by upregulating MnSOD. (2010)
  • Author(s): Kawajiri S, Machida Y, Saiki S, Sato S, Hattori N.
  • Journal Title: Neurosci Lett 481 Pages: 88-91
  • Peer Reviewed
• [Journal Article] PINK1 stabilized by mitochondrial depolarization 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 Cell Biol 189 Pages: 211-221
  • Peer Reviewed
• [Journal Article] PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy. (2010)
  • Author(s): Kawajiri S, Saiki S, Sato S, Sato F, Hatano T, Eguchi H, Hattori N.
  • Journal Title: FEBS Lett 584 Joint first authors Pages: 1073-1079
  • Peer Reviewed
• [Journal Article] PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy. (2010)
  • Author(s): Kawajiri S, Saiki S, Sato S, Sato F, Eguchi H, Hattori N
  • Journal Title: FEBS Letters Volume: 584 Pages: 1073-1079
  • Peer Reviewed
• [Journal Article] PINK1 stabilized by mitochondrial depolarization 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: Journal of Cell Biology Volume: 189 Pages: 211-221
  • Peer Reviewed
• [Journal Article] Zonisamide reduces cell death in SH-SY5Y cells via an anti-apoptotic effect and by upregulating MnSOD. (2010)
  • Author(s): Kawajiri S, Machida Y, Saiki S, Sato S, Hattori N.
  • Journal Title: Neuroscience Letters Volume: 481 Pages: 88-91
  • Peer Reviewed
• [Journal Article] PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy. (2010)
  • Author(s): Kawajiri S, Saiki S, Sato S, Sato F, Eguchi H, Hattori N
  • Journal Title: FEBS Letters (印刷中)
  • Peer Reviewed
• [Presentation] Autophagic regulation by caffeine and its analogues. (2011)
  • Author(s): 斉木臣二
  • Organizer: オートファジー研究会
  • Place of Presentation: ヤマハリゾートつま恋
  • Year and Date: 2011-01-14
• [Presentation] Analysis of whether MITOL associates with the PINK1/parkin-mediated mitophagy. (2010)
  • Author(s): Sumihiro Kawajiri, Shinji Saiki, Shigeto Sato, Shigeru Yanagi, Nobutaka Hattori.
  • Organizer: The 7th Conference of Asian Society for Mitochondrial Research and Medicine (ASMRM) and 10th Conference of Japanese Society for Mitochondrial Research and Medicine (J-mit)
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2010-12-16
• [Presentation] PINK1, parkin, mitochondriaの相互作用の検討 (2010)
  • Author(s): 斉木臣二、河尻澄宏、佐藤栄人、今道洋子、服部信孝
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2010-05-20
• [Presentation] 家族性パーキンソン病原因遺伝子PINK1のmitophagy調節機構について (2010)
  • Author(s): 河尻澄宏、斉木臣二、佐藤栄人、波田野琢、里史明、江口博人、服部信孝
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2010-05-20
• [Presentation] PINK1, parkin, mitochondriaの相互作用の検討 (2010)
  • Author(s): 斉木臣二, 河尻澄宏、佐藤栄人、今道洋子、服部信孝
  • Organizer: 第52回日本神経学会
  • Place of Presentation: 東京(東京国際フォーラム)
  • Year and Date: 2010-05-20
• [Presentation] 家族性パーキンソン病原因遺伝子PINK1のmitophagy調節機構について (2010)
  • Author(s): 河尻澄宏、斉木臣二、佐藤栄人、波田野琢、里史明、江口博人、服部信孝
  • Organizer: 第52回日本神経学会
  • Place of Presentation: 東京(東京国際フォーラム)
  • Year and Date: 2010-05-20
• [Presentation] Caffeine regulates autophagy via mTOR signaling pathway. (2010)
  • Author(s): 斉木臣二、今道洋子、河尻澄宏、服部信孝
  • Organizer: 第5回日本ケミカルバイオロジー学会
  • Place of Presentation: 慶応義塾大学日吉キャンパス協生館
  • Year and Date: 2010-05-18
• [Presentation] 家族性パーキンソン病原因遺伝子PINK1のmitophagy調節機構について (2010)
  • Author(s): 河尻澄宏、斉木臣二、佐藤栄人、波田野琢、里史明、江口博人、服部信孝
  • Organizer: 第18回カテコールアミン研究会
  • Place of Presentation: 品川プリンホテル
  • Year and Date: 2010-04-24
• [Presentation] 家族性パーキンソン病原因遺伝子PINK1のmitophagy調節機構について (2010)
  • Author(s): 河尻澄宏、斉木臣二、佐藤栄人、波田野琢、里史明、江口博人、服部信孝
  • Organizer: 第18回カテコールアミン研究会
  • Place of Presentation: 東京(品川プリンスホテル)
  • Year and Date: 2010-04-24
• [Presentation] PINK1の分解機構の解析 (2009)
  • Author(s): 河尻澄宏、斉木臣二, ら
  • 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
• [Remarks] ホームページ等