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

Karanasios, Eleftherios, Walker, Simon A., Okkenhaug, Hanneke, Manifava, Maria, Hummel, Eric, Zimmermann, Hans, Ahmed, Qashif, Domart, Marie-Charlotte, Collinson, Lucy, Ktistakis, Nicholas T.·2016·Nature Communications
DOI 10.1038/ncomms12420PMC PMC4987534
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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.

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Metadata

Authors
Karanasios, E., Walker, S. A., Okkenhaug, H., Manifava, M., Hummel, E., Zimmermann, H., Ahmed, Q., Domart, M.-C., Collinson, L., & Ktistakis, N. T.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-08-11
Volume
7
Issue
1
ISSN
2041-1723
DOI
10.1038/ncomms12420
PMC
PMC4987534
Cited by
321
References
4
Language
en
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