Study of protein-dependent bulk phospholipid transfer between organelles

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Osawa Takuo 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (00771164)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: オートファジー / 脂質輸送

Outline of Final Research Achievements

The autophagy-related protein Atg2 tethers the endoplasmic reticulum (ER) to the isolation membrane (IM) and transfers phospholipids from the ER to the IM. The mechanism of Atg2-mediated phospholipid transfer has not been elucidated. In this study, we obtained structural information of Atg2 using single particle analysis and AlphaFold2 and used it to investigate how Atg2 transfers phospholipids. Based on the structural information, Atg2 has a long hydrophobic groove for phospholipid binding. Amino acid deletion predicted to narrow the groove of Atg2 reduced the phospholipid transfer activity of Atg2 and impaired autophagy in yeast cells. These results suggest that Atg2 acts as a bridge for phospholipids to move from the ER to the IM.

Free Research Field

構造生物

Academic Significance and Societal Importance of the Research Achievements

細胞が機能を維持する上で、オルガネラ間の脂質のやり取りは必要不可欠である。膜間での大量のリン脂質移動は膜同士の接触によって起こると考えられてきた。本研究成果は、脂質輸送タンパク質によっても大量のリン脂質の移動が起こりうることを示しており、オートファジー分野だけにととどまらず細胞生物学的にも学術的意義が高い。