2025-09-17 北海道大学,東京科学大学,科学技術振興機構
オートファゴソーム新生の模式図。
Atg9小胞と呼ばれる膜小胞を最初の種として、分解標的を取り囲みながら膜が拡大し、閉じてオートファゴソームとなる。オートファゴソームはリソソームと融合し、内容物(たんぱく質やミトコンドリアなど)はリソソーム酵素の働きで分解される。
<関連情報>
- https://www.hokudai.ac.jp/news/2025/09/post-2060.html
- https://www.hokudai.ac.jp/news/pdf/250917_pr.pdf
- https://www.nature.com/articles/s41594-025-01678-3
相分離は、オートファジーの進行に向けてAtg8の脂質化と小胞の凝縮を促進する Phase separation promotes Atg8 lipidation and vesicle condensation for autophagy progression
Yuko Fujioka,Takuma Tsuji,Tetsuya Kotani,Hiroyuki Kumeta,Chika Kakuta,Junko Shimasaki,Toyoshi Fujimoto,Hitoshi Nakatogawa & Nobuo N. Noda
Nature Structural & Molecular Biology Published:16 September 2025
DOI:https://doi.org/10.1038/s41594-025-01678-3
Abstract
Upon starvation, the autophagy-initiating Atg1 complex undergoes phase separation to organize the preautophagosomal structure (PAS) in Saccharomyces cerevisiae, from which autophagosome formation is considered to proceed. However, the physiological roles of the PAS droplet remain unclear. Here we show that core Atg proteins are recruited into early PAS droplets that are formed by phase separation of the Atg1 complex with different efficiencies in vitro. The Atg12–Atg5–Atg16 E3 ligase complex for Atg8 lipidation is the most efficiently condensed in the droplets through specific Atg12–Atg17 interaction, which is also important for the PAS targeting of the E3 complex in vivo. In vitro reconstitution demonstrates that E3-enriched early PAS droplets promote Atg8 lipidation and that Atg8 coating of the vesicle membrane is both necessary and sufficient for their condensation into the droplets. These data suggest that the PAS functions as an efficient production site for lipidated Atg8 and pools membrane seeds to drive autophagosome formation.
