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Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles

Author

Listed:
  • Eleftherios Karanasios

    (Signalling Programme, The Babraham Institute)

  • Simon A. Walker

    (Signalling Programme, The Babraham Institute)

  • Hanneke Okkenhaug

    (Signalling Programme, The Babraham Institute)

  • Maria Manifava

    (Signalling Programme, The Babraham Institute)

  • Eric Hummel

    (Carl Zeiss Microscopy GmbH)

  • Hans Zimmermann

    (Carl Zeiss Microscopy GmbH)

  • Qashif Ahmed

    (Signalling Programme, The Babraham Institute)

  • Marie-Charlotte Domart

    (The Francis Crick Institute)

  • Lucy Collinson

    (The Francis Crick Institute)

  • Nicholas T. Ktistakis

    (Signalling Programme, The Babraham Institute)

Abstract

Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment.

Suggested Citation

  • Eleftherios Karanasios & Simon A. Walker & Hanneke Okkenhaug & Maria Manifava & Eric Hummel & Hans Zimmermann & Qashif Ahmed & Marie-Charlotte Domart & Lucy Collinson & Nicholas T. Ktistakis, 2016. "Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles," Nature Communications, Nature, vol. 7(1), pages 1-17, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12420
    DOI: 10.1038/ncomms12420
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    Cited by:

    1. Paula P. Coelho & Geoffrey G. Hesketh & Annika Pedersen & Elena Kuzmin & Anne-Marie N. Fortier & Emily S. Bell & Colin D. H. Ratcliffe & Anne-Claude Gingras & Morag Park, 2022. "Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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