Elucidation of Novel Ubiquinone Regulatory Mechanisms for the Treatment of Heart Failure

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20660
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Hirose Kentaro 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (70958355)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 心不全 / ユビキノン / コエンザイムQ / マウス

Outline of Final Research Achievements

Ubiquinone(UQ) is a redox-active molecule, essential for mitochondrial respiration. UQ administration is expected to improve heart failure, but the intercellular regulation of UQ has not been well understood. In this study, we focused on Coenzyme Q10a (Coq10a) gene, which is predicted to possess a UQ-binding site. Toward an understanding of Coq10a function, we generated the first Coq10a knockout and heart-specific knockout mice. These mutants consistently developed cardiac growth postnatally. We measured UQ levels in cardiac tissues, detecting profound UQ elevation in the KO hearts. Interestingly, the elevation of UQ amounts seems to ectopically activate PPAR signaling through the potential binding to PPAR protein, leading to cardiac overgrowth. Taken together, our study provided the first evidence that the loss of a UQ chaperone leads to the overgrowth of postnatal hearts through dysregulation of UQ levels.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

多機能分子であるユビキノン(UQ)は、電子伝達系におけるATP産生や酸化ストレスからの細胞保護としての機能がある。心不全の心臓組織において、UQ存在量が大きく低下する為、経口投与が心不全への予防・治療効果を示すことが知られる。ただし、細胞内におけるUQの制御機構はあまり分かっていない。本研究では、心臓におけるUQ量の制御に関わるUQシャペロンの存在を初めて見出した。この成果は、UQを介した心不全治療法を提示できる可能性がある。