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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
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    References listed on IDEAS

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