Development of drug delivery system to mitochondria and a drug for the treatment of mitochondrial disease

• Project/Area Number: 16K15482
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Tomizawa Kazuhito 熊本大学, 大学院生命科学研究部(医), 教授 (40274287)
• Co-Investigator(Renkei-kenkyūsha): ANDO Yukio 熊本大学, 大学院生命科学研究部, 教授 (20253742)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ミトコンドリア / DDS / 糖尿病 / ミトコンドリア病 / リポソーム / 脳・神経 / 脳神経疾患 / 薬剤送達 / 生理学

Outline of Final Research Achievements

We generated the peptides consisting of mitochondrial localizing signal peptide derived from Cdk5rap1 and poly arginine (9R). We incubated primary cultured myocardial cells, skeletal muscle cels and neurons with the peptides. The peptides were localized on mitochondria. Moreover, we generated the liposomes containing eperisone, which are conjugated with the mitocondrial signal peptide. When applied the liposomes to Cdk5rap1-deficient skeletal muscle cells, the liposomes were localized in mitochondria and mitochondrial functions such as compel activities, mitochondrial membrane potential and the translation of mitochondrial proteins were improved.

Research Products

• [Int'l Joint Research] パドバ大学(イタリア)
• [Journal Article] Defective Mitochondrial tRNA Taurine Modification Activates Global Proteostress and Leads to Mitochondrial Disease. (2018)
  • Author(s): Fakruddin M, Wei FY, Suzuki T, Asano K, Kaieda T, Omori A, Izumi R, Fujimura A, Kaitsuka T, Miyata K, Araki K, Oike Y, Scorrano L, Suzuki T, Tomizawa K.
  • Journal Title: Cell Rep. Volume: 22 Issue: 2 Pages: 482-496
  • DOI: 10.1016/j.celrep.2017.12.051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion. (2017)
  • Author(s): Takahashi, N., Wei, F.-Y., Watanabe, S., Hirayama, M., Ohuchi, Y., Fujimura, A., Kaitsuka, T., Sawa, T., Nakayama, H., Akaike, T. and Tomizawa, K.
  • Journal Title: Nucl. Acid Res. Volume: 45 Pages: 435-445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Taurine-modification of mitochondrial tRNA is essential for translation and controls proteostasis network via Opa1. (2017)
  • Author(s): Tomizawa, K.
  • Organizer: Cold Spring Harbor Asia “RNA modifications & Epitranscriptomics”
  • Int'l Joint Research / Invited
• [Remarks] 熊本大学大学院生命科学研究部・分子生理学分野ホームページ
  • URL: http://kumamoto-physiology.jp