Impact of Intracellular Quality Control in Heart Failure by Selective Endoplasmic Reticulum Degradation of ER-Phagy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17572
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Misaka Tomofumi 福島県立医科大学, 医学部, 助教 (50793080)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 心不全 / 細胞内品質管理 / オートファジー

Outline of Final Research Achievements

Recently, the existence of autophagy-mediated selective endoplasmic reticulum degradation (ER-phagy) has been demonstrated, but its role in the heart has not been investigated. In failing hearts 4 weeks after transverse aortic constriction, the accumulation of ubiquitin-positive proteins, P62-positive proteins, and defective proteins was suggested. mRNA levels of ER-phagy-related molecule X were significantly decreased in failing hearts after aortic constriction, suggesting that it is involved in the development of heart failure, but its functional significance needs further investigation. Besides, mass spectrometry analysis suggested that myristoylation of autophagy-related proteins is associated with ER-phagy, which is expected to be a novel mechanism.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

心不全の病態において不良なタンパク質の蓄積が役割を果たしていることから、心不全の発症と進展を防ぐために心筋細胞内の恒常性維持機構としてのERファジーが新しい治療ターゲットと期待されている。本研究により、オートファジーに関連するタンパク質のミリストイル化がERファジーに関連することが示唆され、これが新規メカニズムであることが明らかになった。本研究成果からERファジーに関わる新規分子機構の可能性が明らかとなり、心不全に対する新たな治療戦略となり得ると期待され、今後の検討が必要である。