Physiological role of mitochondrial heterogeneity in ventricular myocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06869
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: University of Fukui
• Principal Investigator: Takeuchi Ayako 福井大学, 学術研究院医学系部門, 准教授 (00378704)
• Co-Investigator(Kenkyū-buntansha): 嶋吉 隆夫 九州大学, 情報基盤研究開発センター, 准教授 (60373510)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心室筋細胞 / ミトコンドリア / トランスポータ

Outline of Final Research Achievements

The purpose of the study was to clarify physiological roles of functional heterogeneity of mitochondria in ventricular myocytes. We obtained following results. 1. mitochondrial Na-Ca exchanger (NCLX) was localized near sarcoplasmic reticulum SERCA2>sarcoplasmic reticulum RyR>sarcolemmal Na-K ATPase, 2. NCLX was electrogenic, and reverse mode of Na-Ca exchange activity was much slower than forward mode, 3. mitochondrial membrane was more depolarized and response to uncoupler FCCP was slower at cellular edge than those at central part. Then we constructed a new mathematical model of ventricular myocyte which can calculate pH and mitochondrial ion dynamics, to analyze mechanisms explaining experimental data.

Free Research Field

細胞生理学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、ミトコンドリアNa-Ca交換（NCLX）が起電性であることが証明され、起電性か否かという長年の議論に終止符をうつことができた。また、心室筋細胞内の部位によるミトコンドリア機能の不均一性は、特に心不全などの細胞内構造のリモデリング時に重要となると予想される。今後の研究展開によって、ミトコンドリア機能の不均一性をターゲットとした新たな細胞機能制御法の開発につながると考える。