Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy

Tabata, Keisuke; Imai, Kenta; Fukuda, Koki; Yamamoto, Kentaro; Kunugi, Hayato; Fujita, Toshiharu; Kaminishi, Tatsuya; Tischer, Christian; Neumann, Beate; Reither, Sabine; Verissimo, Fatima; Pepperkok, Rainer; Yoshimori, Tamotsu; Hamasaki, Maho

doi:https://doi.org/10.1038/s41467-024-51402-w

Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy

Tabata, Keisuke; Imai, Kenta; Fukuda, Koki et al.

Nature Communications, 2024, 15, 7194

Number of Access:1,153（2025-08-16 00:38 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98257

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Title	Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy
Creator	NRID 1000040569018 1000040569018 researchmap permalink read0155313 read0155313 Scopus Author ID 26041137700 26041137700 CreatorName Tabata, Keisuke
	CreatorName Imai, Kenta
	CreatorName Fukuda, Koki
	CreatorName Yamamoto, Kentaro
	CreatorName Kunugi, Hayato
	CreatorName Fujita, Toshiharu
	NRID 1000010391921 1000010391921 researchmap permalink TKaminishi TKaminishi Scopus Author ID 14830588900 14830588900 CreatorName Kaminishi, Tatsuya
	CreatorName Tischer, Christian
	CreatorName Neumann, Beate
	CreatorName Reither, Sabine
	CreatorName Verissimo, Fatima
	CreatorName Pepperkok, Rainer
	NRID 1000060191649 1000060191649 researchmap permalink read0085516 read0085516 Scopus Author ID 7006810223 7006810223 CreatorName Yoshimori, Tamotsu
	NRID 1000030455216 1000030455216 ORCID 0000-0002-5646-5136 0000-0002-5646-5136 researchmap permalink _maho-hamasaki _maho-hamasaki Scopus Author ID 7006462157 7006462157 CreatorName Hamasaki, Maho
Description	Tabata K., Imai K., Fukuda K., et al. Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy. Nature Communications 15, 7194 (2024); https://doi.org/10.1038/s41467-024-51402-w.
Abstract	Autophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by a double-membrane organelle called autophagosome and degrading materials by fusing with the lysosome. The process of autophagy is regulated by sequential recruitment and function of autophagy-related (Atg) proteins. Genetic hierarchical analyses show that the ULK1 complex comprised of ULK1-FIP200-ATG13-ATG101 translocating from the cytosol to autophagosome formation sites as a most upstream ATG factor; this translocation is critical in autophagy initiation. However, how this translocation occurs remains unclear. Here, we show that ULK1 is palmitoylated by palmitoyltransferase ZDHHC13 and translocated to the autophagosome formation site upon autophagy induction. We find that the ULK1 palmitoylation is required for autophagy initiation. Moreover, the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate, one of the autophagosome membrane’s lipids. Our results reveal how the most upstream ULK1 complex translocates to the autophagosome formation sites during autophagy.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	15
Page	7194
Date of Issued	2024-10-03
Language	English
Handle URL	https://hdl.handle.net/11094/98257
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-024-51402-w
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Nature Communications. 2024, 15, p. 7194
DC.title	Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy
DC.creator	Tabata, Keisuke
	Imai, Kenta
	Fukuda, Koki
	Yamamoto, Kentaro
	Kunugi, Hayato
	Fujita, Toshiharu
	Kaminishi, Tatsuya
	Tischer, Christian
	Neumann, Beate
	Reither, Sabine
	Verissimo, Fatima
	Pepperkok, Rainer
	Yoshimori, Tamotsu
	Hamasaki, Maho
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-03
DC.identifier	https://doi.org/10.1038/s41467-024-51402-w
DC.description	Tabata K., Imai K., Fukuda K., et al. Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy. Nature Communications 15, 7194 (2024); https://doi.org/10.1038/s41467-024-51402-w.
DCTERMS.abstract	Autophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by a double-membrane organelle called autophagosome and degrading materials by fusing with the lysosome. The process of autophagy is regulated by sequential recruitment and function of autophagy-related (Atg) proteins. Genetic hierarchical analyses show that the ULK1 complex comprised of ULK1-FIP200-ATG13-ATG101 translocating from the cytosol to autophagosome formation sites as a most upstream ATG factor; this translocation is critical in autophagy initiation. However, how this translocation occurs remains unclear. Here, we show that ULK1 is palmitoylated by palmitoyltransferase ZDHHC13 and translocated to the autophagosome formation site upon autophagy induction. We find that the ULK1 palmitoylation is required for autophagy initiation. Moreover, the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate, one of the autophagosome membrane’s lipids. Our results reveal how the most upstream ULK1 complex translocates to the autophagosome formation sites during autophagy.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98257
citation_title	Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy
citation_author	Tabata, Keisuke
	Imai, Kenta
	Fukuda, Koki
	Yamamoto, Kentaro
	Kunugi, Hayato
	Fujita, Toshiharu
	Kaminishi, Tatsuya
	Tischer, Christian
	Neumann, Beate
	Reither, Sabine
	Verissimo, Fatima
	Pepperkok, Rainer
	Yoshimori, Tamotsu
	Hamasaki, Maho
citation_publisher	Nature Research
citation_language	English
citation_date	2024-10-03
citation_journal_title	Nature Communications
citation_volume	15
citation_firstpage	7194
citation_doi	https://doi.org/10.1038/s41467-024-51402-w
citation_public_url	https://hdl.handle.net/11094/98257

Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy

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