Development of quantitative measurement method of ATP production rate in mitochondria in mouse

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22513
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: National Cardiovascular Center Research Institute (2020-2021); Kyoto University (2019)
• Principal Investigator: Yamamoto Masamichi 国立研究開発法人国立循環器病研究センター, 研究所, 特任部長 (70423150)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: アデノシン三リン酸 / エネルギー代謝 / イメージング

Outline of Final Research Achievements

There is a great need in the life science field for "a robust technology that can quantitatively measure the rate of ATP (adenosine triphosphate) production in mitochondria in vivo," but there has been no core technology to meet this need. The reason for this is that it is not possible to directly measure the amount of ATP in mitochondria.
In this study, we created a new ATP sensor protein, CR-ATeam, as a technology to measure ATP dynamics in mitochondria by experimenting with various fluorescent proteins that improve the brightness value of ATP. We also tried to generate mice by using various constructs. As a result, we succeeded in generating a new mouse that expresses ATeam in the mitochondrial matrix.

Free Research Field

代謝イメージング

Academic Significance and Societal Importance of the Research Achievements

高輝度のATPセンサー蛍光タンパク質であるCR-ATeamが作成され、低発現量でATP動態をFRET変化として計測できるプローブができた。
また、世界で初めて、ミトコンドリアマトリックス内で産生されるATP動態を生体内で計測できるマウスを作出した。これにより、生体内のミトコンドリア内ATP動態をin vitroだけでなくin vivoでも定量的に解析できるようになる。このマウスを用いれば、様々な疾患評価だけでなく薬剤評価などへも応用できると期待される。