相分離による酵素反応の促進機構：Atg8の脂質化反応を例に

• Published in: 日本薬理学会年会要旨集 p. 2-B-S30-3
• Main Author: 藤岡, 優子
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: protein; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_2-B-S30-3

Autophagy is an intracellular degradation system that contributes not only to securing nutrient source during starvation, but also to intracellular clearance under normal conditions. Upon starvation, a new lipid membrane called the isolation membrane is generated from the pre-autophagosome structure (PAS), which is the starting point of autophagy, and forms a double membrane autophagosome by wrapping around a portion of the cytoplasm. We were the first to identify that PAS is a droplet formed by the liquid-liquid phase separation of the Atg protein. However, it is still unclear what kind of reactions occur in PAS using the droplet characteristics. We performed an in vitro analysis of the introduction of downstream Atg proteins into the initial PAS droplets formed by purified Atg1 complex and found that the efficiency of introduction into the droplets varied among Atg proteins. Interestingly, the Atg12-Atg5-Atg16 complex, the E3 enzyme of the lipid-binding reaction system of the autophagy core factor Atg8, was significantly enriched in the droplet, whereas Atg4, the delipidase of Atg8, was not, thus promoting the formation of lipidated Atg8 in the droplet. One of the reasons why PAS is a droplet may be that it provides an efficient site for enzymatic reactions essential for autophagy to occur.