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A novel approach to elucidate mitochondrial functions with mitochondria-targeted opsins

Research Project

Project/Area Number 17K19437
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Neuroscience and related fields
Research InstitutionTohoku University

Principal Investigator

ISHIZUKA Toru  東北大学, 生命科学研究科, 講師 (10344714)

Research Collaborator YAWO Hiromu  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsミトコンドリア / オプトジェネティクス / プロトンポンプ / ロドプシン / ターゲティングシグナル / 光駆動プロトンポンプ / 微生物型ロドプシン / 光遺伝学 / オルガネラ
Outline of Final Research Achievements

We successfully identified a novel mitochondria-targeting signal (tentatively named Mito-X signal). When the Mito-X signal was conjugated with a light-driven proton pump ArchT, the protein (ArchT(Mito)) was expressed effectively in mitochondria. Immunocytochemical staining revealed that the expression of ArchT(Mito) was well overlaid with that of the mitochondrial marker molecule such as TOMM22 and ATP5A1. A preliminary physiological experiment showed that the ArchT(Mito) was inserted into an inner membrane of mitochondria with an appropriate orientation. Futher experiments requires that the ArchT(Mito) actually generates a proton gradient across the inner mitochondrial membrane with light.

Academic Significance and Societal Importance of the Research Achievements

これまで主にニューロンの活動制御の手段として用いられてきたオプトジェネティクスが,本研究の成果により細胞内小器官のひとつであるミトコンドリアに効率よく分子ツールをターゲティングさせるシグナルの発見に成功し,新たな分子ツールを創出したことで,薬理学的手法では実現が困難であった可逆的かつ時空間分解能に優れた新たな次元のミトコンドリア細胞生理学研究やミトコンドリア変性に伴う様々な病態の原因解明・治療法の開発研究(ミトコンドリアオプトジェネティクス)への展開とその発展が期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Optogenetic study of the response interaction among multi-afferent inputs in the barrel cortex of rats.2019

    • Author(s)
      Liu Y, Ohshiro T, Sakuragi S, Koizumi K, Mushiake H, Ishizuka T, Yawo H.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 3917-3917

    • DOI

      10.1038/s41598-019-40688-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Organelle Optogenetics: Direct Manipulation of Intracellular Ca2+ Dynamics by Light2018

    • Author(s)
      Toshifumi Asano、Hiroyuki Igarashi、Toru Ishizuka、Hiromu Yawo
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12 Pages: 561-561

    • DOI

      10.3389/fnins.2018.00561

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-07-21   Modified: 2020-03-30  

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