IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51402-w.html
   My bibliography  Save this article

Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy

Author

Listed:
  • Keisuke Tabata

    (Osaka University
    Osaka University)

  • Kenta Imai

    (Osaka University
    Osaka University)

  • Koki Fukuda

    (Osaka University
    Osaka University)

  • Kentaro Yamamoto

    (Osaka University
    Osaka University)

  • Hayato Kunugi

    (Osaka University
    Osaka University)

  • Toshiharu Fujita

    (Osaka University
    Osaka University)

  • Tatsuya Kaminishi

    (Osaka University
    Osaka University)

  • Christian Tischer

    (EMBL)

  • Beate Neumann

    (EMBL)

  • Sabine Reither

    (EMBL)

  • Fatima Verissimo

    (EMBL)

  • Rainer Pepperkok

    (EMBL
    EMBL)

  • Tamotsu Yoshimori

    (Osaka University
    Osaka University
    Osaka University)

  • Maho Hamasaki

    (Osaka University
    Osaka University)

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.

Suggested Citation

  • Keisuke Tabata & Kenta Imai & Koki Fukuda & Kentaro Yamamoto & Hayato Kunugi & Toshiharu Fujita & Tatsuya Kaminishi & Christian Tischer & Beate Neumann & Sabine Reither & Fatima Verissimo & Rainer Pep, 2024. "Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51402-w
    DOI: 10.1038/s41467-024-51402-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51402-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51402-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yijian Rao & Marco G. Perna & Benjamin Hofmann & Viola Beier & Thomas Wollert, 2016. "The Atg1–kinase complex tethers Atg9-vesicles to initiate autophagy," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    2. Shuyang Chen & Bo Zhu & Chengqian Yin & Wei Liu & Changpeng Han & Baoen Chen & Tongzheng Liu & Xin Li & Xiang Chen & Chunying Li & Limin Hu & Jun Zhou & Zhi-Xiang Xu & Xiumei Gao & Xu Wu & Colin R. Go, 2017. "Palmitoylation-dependent activation of MC1R prevents melanomagenesis," Nature, Nature, vol. 549(7672), pages 399-403, September.
    3. Maho Hamasaki & Nobumichi Furuta & Atsushi Matsuda & Akiko Nezu & Akitsugu Yamamoto & Naonobu Fujita & Hiroko Oomori & Takeshi Noda & Tokuko Haraguchi & Yasushi Hiraoka & Atsuo Amano & Tamotsu Yoshimo, 2013. "Autophagosomes form at ER–mitochondria contact sites," Nature, Nature, vol. 495(7441), pages 389-393, March.
    4. A. Scotto Rosato & S. Montefusco & C. Soldati & S. Di Paola & A. Capuozzo & J. Monfregola & E. Polishchuk & A. Amabile & C. Grimm & A. Lombardo & M. A. De Matteis & A. Ballabio & D. L. Medina, 2019. "TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    5. Keisuke Tabata & Vibhu Prasad & David Paul & Ji-Young Lee & Minh-Tu Pham & Woan-Ing Twu & Christopher J. Neufeldt & Mirko Cortese & Berati Cerikan & Yannick Stahl & Sebastian Joecks & Cong Si Tran & C, 2021. "Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Elodie Mailler & Carlos M. Guardia & Xiaofei Bai & Michal Jarnik & Chad D. Williamson & Yan Li & Nunziata Maio & Andy Golden & Juan S. Bonifacino, 2021. "The autophagy protein ATG9A enables lipid mobilization from lipid droplets," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Do-Won Jeong & Jong-Wan Park & Kyeong Seog Kim & Jiyoung Kim & June Huh & Jieun Seo & Ye Lee Kim & Joo-Youn Cho & Kwang-Woong Lee & Junji Fukuda & Yang-Sook Chun, 2023. "Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Nell Saunders & Blandine Monel & Nadège Cayet & Lorenzo Archetti & Hugo Moreno & Alexandre Jeanne & Agathe Marguier & Julian Buchrieser & Timothy Wai & Olivier Schwartz & Mathieu Fréchin, 2024. "Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Ji-Man Park & Da-Hye Lee & Do-Hyung Kim, 2023. "Redefining the role of AMPK in autophagy and the energy stress response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Liv Zimmermann & Xiaohan Zhao & Jana Makroczyova & Moritz Wachsmuth-Melm & Vibhu Prasad & Zach Hensel & Ralf Bartenschlager & Petr Chlanda, 2023. "SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Chengyang Li & Patrick Duckney & Tong Zhang & Yanshu Fu & Xin Li & Johan Kroon & Geert Jaeger & Yunjiang Cheng & Patrick J. Hussey & Pengwei Wang, 2022. "TraB family proteins are components of ER-mitochondrial contact sites and regulate ER-mitochondrial interactions and mitophagy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Viola Nähse & Camilla Raiborg & Kia Wee Tan & Sissel Mørk & Maria Lyngaas Torgersen & Eva Maria Wenzel & Mireia Nager & Veijo T. Salo & Terje Johansen & Elina Ikonen & Kay Oliver Schink & Harald Stenm, 2023. "ATPase activity of DFCP1 controls selective autophagy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51402-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.