Elucidation of the mitochondrial ubiquitination signal transduction system

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20637
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Gakushuin University
• Principal Investigator: ITO Naoki 学習院大学, 理学部, 研究員 (20965834)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: ミトコンドリア / ユビキチン修飾 / ユビキチンリガーゼ / 脱ユビキチン化

Outline of Final Research Achievements

Mitochondria play a pivotal role not only in ATP production but also as a relay station for various intracellular signal transductions. In this study, we concentrated on MITOL, a major mitochondrial ubiquitin ligase, with the primary objective of elucidating the physiological role of ubiquitination and the mechanism of ubiquitin chain addition with different actions. The analysis indicated that MITOL plays a role in maintaining respiratory capacity by facilitating iron supply to mitochondria through ubiquitination of HMOX2 in the endoplasmic reticulum. Additionally, it was observed that MITOL may collaborate with the deubiquitinating enzyme OTUD4 to determine the type of ubiquitin chain to be added to Parkin.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

MITOLが小胞体上のHMOX2を介してヘム分解を促進し、ミトコンドリアへの鉄供給を制御するという発見は、これまで不明瞭だった鉄供給機構の解明にとどまらず、ミトコンドリアをハブとしたオルガネラ連携の新たな事例ともなり、ミトコンドリア、小胞体、生命金属研究の発展に寄与すると考えられる。また、MITOLとOTUD4の解析結果は様々な場所で起こるユビキチン修飾に共通した普遍的課題であるユビキチン鎖の種類の使い分け、決定因子の謎を解決する糸口となる。