Establishment of multi-cell / multi-organ linkage analysis method using cardiomyocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19395
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: National Institutes of Natural Sciences
• Principal Investigator: Nishida Motohiro 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 教授 (90342641)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 臓器連関 / 心臓 / ミトコンドリア / 超硫黄化 / 恒常性維持

Outline of Final Research Achievements

We established an experimental system to analyze multi-organ and multicellular communication using a cell-type-specific protein labeling method in MetRSL274G-expressing mice. Using a cardiac disease model in mice, we discovered that mitochondria-related proteins originating from the myocardium are transported to the kidneys. Based on previous reports suggesting that the decline in mitochondrial quality promotes the release of mitochondria from cardiomyocytes, we investigated the regulatory mechanisms of mitochondrial quality in cardiomyocytes. We also revealed that persulfide molecules play a role in protecting mitochondrial quality. Furthermore, the persulfidation of mitochondria-related proteins is significantly altered in the hearts of cardiac disease model mice.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

生体内の臓器や組織は個々に機能するわけでなく、様々な臓器・組織との相互作用を介して生体の高次機能を維持している。心臓移植後の患者で報告されている「心臓の記憶」もまた臓器連関を示唆する例であるが、心臓が多臓器に与える情報については不明であった。病気の心臓がミトコンドリア関連タンパク質を腎臓などに輸送することを初めて明らかにした点は心臓原生の臓器連関の仕組みを読み解く糸口になるとともに、ミトコンドリアの品質維持を標的とする疾患診断マーカーや予防・治療法の開発につながる可能性が期待できる。