Analysis of the relationship between an accumulation of mutant mtDNA and the mitochondrial quality control in Parkinsonism

• Project/Area Number: 15K21081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; Laboratory animal science
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Fuke Satoshi 滋賀医科大学, 医学部, 助教 (20422660)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ミトコンドリア / パーキンソン病 / ミトコンドリアDNA / Parkin / Polg / mitochondria / mtDNA

Outline of Final Research Achievements

To elucidate the physiological significance of relationships between an accumulation of mutant mtDNA molecules and the mitochondrial quality control depending on mitophagy in Parkinson’s disease, a role of mitophagy due to Parkin in mtDNA dynamics was assessed. In a mouse neuroblastoma cell line (Neuro2a), we found that there are not a few Parkin-nonlocalized mitochondria that were undegraded after the induction of mitophagy by FCCP mitochondrial depolarizing agent. These result suggest that the mitochondrial depolarization is necessary but not enough for the removal of damaged mitochondria through mitophagy.

Research Products

• [Journal Article] Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder (2016)
  • Author(s): Kasahara T, Ishiwata M, Kakiuchi C, Fuke S, Iwata N, Ozaki N, Kunugi H, Minabe Y, Nakamura K, Iwata Y, Fujii K, Kanba S, Ujike H, Kusumi I, Kataoka M, Matoba N, Takata A, Iwamoto K, Yoshikawa T, Kato T
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: - Issue: 8 Pages: 518-529
  • DOI: 10.1111/pcn.12496
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The local accumulation of mtDNA deletions in the brain and behavioral abnormalities in heterozygous Polg mutant mice. (2016)
  • Author(s): Satoshi Fuke, Yasufumi Shigeyoshi, Natsu Koyama, Mie Kubota-Sakashita, Seiji Hitoshi, Tadafumi Kato
  • Organizer: The 13th Conference of Asian Society for Mitochondrial Research and Medicine & The 16th Conference of Japanese Society of Mitochondrial Research and Medicine
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-10-30
  • Int'l Joint Research
• [Presentation] A heterozygous mutation of Polg gene causes behavioral abnormalities due to the tissue-specific accumulation of multiple mtDNA deletions in mice. (2015)
  • Author(s): Satoshi Fuke
  • Organizer: BMB2015（第38回日本分子生物学会年回 第88回日本生化学会大会）
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Book] 日本臨牀 73巻増刊号 “免疫性神経疾患と神経幹細胞” (2015)
  • Author(s): 福家 聡
  • Total Pages: 9
  • Publisher: 日本臨牀社
• [Book] 医学のあゆみ “免疫性神経疾患の病態・治療と神経幹細胞” (2015)
  • Author(s): 福家 聡
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社