• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Drug development for mitochondrial disease based on sulfur metabolism

Research Project

Project/Area Number 18K19521
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionTohoku University (2019)
Kumamoto University (2018)

Principal Investigator

Wei Fanyan  東北大学, 加齢医学研究所, 教授 (90555773)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsミトコンドリア / ミトコンドリア病 / tRNA / 硫黄修飾 / 硫黄 / MELAS
Outline of Final Research Achievements

Mitochondrial disease is a devastating genetic disease, which is mainly caused by the pathogenic mutations in mitochondrial DNA. Currently, there is no effective treatment that can cure the disease. This study is aimed to develop a functional screening system that leads to the discovery of drug target for the treatment of mitochondrial disease. In this study, we utilized a genome-wide shRNA lentiviral system and screened over 3,000 mitochondria-related genes in cell lines carrying pathogenic mitochondria DNA. We discovered a specific shRNA, which targets a gene involved in sulfur metabolism, was capable to upregulate mitochondrial reactive sulfur species as well as respiratory activity, thereby leading to an efficient energy metabolism. These results thus lay the foundation for novel and innovative drug development in near future.

Academic Significance and Societal Importance of the Research Achievements

本研究から、硫黄代謝に関わる遺伝子がミトコンドリア病創薬において有力な標的であることが示唆された。今後は同遺伝子の抑制が個体においてもミトコンドリア機能改善効果を有するかを検証するとともに、同遺伝子産物に対する低分子阻害剤の開発を進める予定である。これらの研究開発により、ミトコンドリア機能を根底から改善しうる薬剤の創出が可能となり、指定難病であるミトコンドリア病に新たな希望をもたらすことができる。

Report

(2 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Regulation of mitochondrial iron homeostasis by sideroflexin 2.2019

    • Author(s)
      Mon EE, Wei FY, Ahmad RNR, Yamamoto T, Moroishi T, Tomizawa K.
    • Journal Title

      J Physiol Sci.

      Volume: 69 Issue: 2 Pages: 359-373

    • DOI

      10.1007/s12576-018-0652-2

    • NAID

      40021819064

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease2018

    • Author(s)
      Asano Kana、Suzuki Takeo、Saito Ayaka、Wei Fan-Yan、Ikeuchi Yoshiho、Numata Tomoyuki、Tanaka Ryou、Yamane Yoshihisa、Yamamoto Takeshi、Goto Takanobu、Kishita Yoshihito、Murayama Kei、Ohtake Akira、Okazaki Yasushi、Tomizawa Kazuhito、Sakaguchi Yuriko、Suzuki Tsutomu
    • Journal Title

      Nucleic Acids Res.

      Volume: 46 Issue: 4 Pages: 1565-1583

    • DOI

      10.1093/nar/gky068

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] tRNA modification in mitochondria disease.2018

    • Author(s)
      魏范研
    • Organizer
      15th Conference of the Asian Society of Mitochondrial Research and Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-07-25   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi