An analysis of mechanism of mitochondria clearance by alternative autophagy during erythrocyte differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Honda Shinya 東京医科歯科大学, 難治疾患研究所, プロジェクト講師 (90532672)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: オートファジー

Outline of Final Research Achievements

Using erythrocytes and mouse embryonic fibroblasts (MEF), we investigated candidate molecules related to mitochondrial removal and alternative autophagy-related molecules by comprehensive proteome analysis. In addition, a detailed analysis of ubiquitin ligase, an alternative autophagy-related molecule that had previously been identified, was performed.
Unfortunately, the candidate molecules identified in the analysis using erythrocytes had no effect on mitochondrial clearance. However, analysis using MEF led to the identification of a new candidate molecule that could be a novel marker for alternative autophagy.
In addition, it has been known that knockdown of alternative autophagy-related ubiquitin ligase results in abnormal Golgi morphology. The search for binding molecules revealed that intracellular enzymes are involved in the maintenance of Golgi morphology.

Free Research Field

オートファジー

Academic Significance and Societal Importance of the Research Achievements

本研究から、新たに新規オートファジーマーカー候補分子が同定された。新規オートファジーは未だマーカーとなる分子は同定されておらず、本研究で同定されたものがマーカーとして利用可能であれば、新規オートファジー研究が飛躍的に発展し、それにより疾患との関連なども明らかになると考えられる。
また、ユビキチンリガーゼとゴルジ体の形態に関しても、新たな関連分子が明らかになったことから、ユビキチン化によるゴルジ体形態維持のより詳細なメカニズムが明らかになっていくと考えられる。