Fundamental Research for the Development of Novel Therapeutic Agents for Mitochondrial Diseases by Stabilizing Regulators of ATP Production

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Osaka University
• Principal Investigator: Kato Hisakazu 大阪大学, 大学院医学系研究科, 助教 (30589312)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ミトコンドリア病 / ATP / タンパク質分解 / ミトコンドリア

Outline of Final Research Achievements

We identified a compound that enhances ATP production by inhibiting the protein degradation of the ATP production regulator G0S2. In this study, we verified the mechanism of action of this compound and its validity as a therapeutic agent for mitochondrial diseases. We found that the compound covalently binds to one amino acid within G0S2, and partly elucidated the mechanism of inhibition of its degradation. We confirmed that G0S2 is expressed in cells derived from patients of mitochondrial diseases and raised the possibility of therapeutic intervention for mitochondrial diseases. We have succeeded in developing a compound that can be administered in vivo by structural optimization, and will proceed with the therapeutic effects of this compound in patient-derived cells and administration to animal models that we already possess and are breeding.

Free Research Field

分子心臓学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリア病は、ミトコンドリアATP合成の低下により細胞死を引き起こし様々な臓器機能の低下を引き起こす希少疾患である。ミトコンドリア病の本質的な治療薬は未だ開発されていない。本研究で明らかにしたATP合成酵素活性化剤は、直接的に細胞内ATPを増産できる点において、画期的なミトコンドリア病の治療薬開発につながることが期待される。