Phase separation promotes Atg8 lipidation and vesicle condensation for autophagy progression

Fujioka, Yuko; Tsuji, Takuma; Kotani, Tetsuya; Kumeta, Hiroyuki; Kakuta, Chika; Shimasaki, Junko; Fujimoto, Toyoshi; Nakatogawa, Hitoshi; Noda, Nobuo N

Phase separation promotes Atg8 lipidation and vesicle condensation for autophagy progression

Fujioka, Yuko; Tsuji, Takuma; Kotani, Tetsuya et al.

Nature structural & molecular biology, 2025, 32(11), 2285-2295

Permalink : https://hdl.handle.net/2115/98060

このアイテムのアクセス数:162件（2026-10-17 05:34 集計）

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Supplementary_Tables	pdf	253 KB	34	Supplementary information
ExtendedData	pdf	2.44 MB	57	Source data

論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/98060
タイトル	Phase separation promotes Atg8 lipidation and vesicle condensation for autophagy progression
著者	Fujioka, Yuko ; Tsuji, Takuma ; Kotani, Tetsuya ; Kumeta, Hiroyuki ; Kakuta, Chika ; Shimasaki, Junko ; Fujimoto, Toyoshi ; Nakatogawa, Hitoshi ; Noda, Nobuo N
e-Rad_Researcher 80399964 著者名 Fujioka, Yuko
e-Rad_Researcher 40725628 著者名 Tsuji, Takuma
著者名 Kotani, Tetsuya
e-Rad_Researcher 00399966 著者名 Kumeta, Hiroyuki
著者名 Kakuta, Chika
著者名 Shimasaki, Junko
著者名 Fujimoto, Toyoshi
著者名 Nakatogawa, Hitoshi
e-Rad_Researcher 40396297 著者名 Noda, Nobuo N
言語	英語
キーワード	Autophagy
	Enzyme mechanisms
	Ubiquitylation
発行日	2025-09-16
出版者	Nature Publishing Group
収録物名	Nature structural & molecular biology
巻(号)	32(11)
ページ	2285-2295
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41594-025-01678-3
PISSN	1545-9985
関連情報	PMID 40957983
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/s41594-025-01678-3