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  Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation

Sawa-Makarska, J., Baumann, V., Coudevylle, N., von Bülow, S., Nogellova, V., Abert, C., et al. (2020). Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation. Science, 369(6508): eaaz7714. doi:10.1126/science.aaz7714.

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Sawa-Makarska, Justyna1, Author
Baumann, Verena1, Author
Coudevylle, Nicolas1, Author
von Bülow, Sören2, Author              
Nogellova, Veronika1, Author
Abert, Christine1, Author
Schuschnig, Martina1, Author
Graef, Martin3, 4, Author
Hummer, Gerhard2, 5, Author              
Martens, Sascha1, Author
Affiliations:
1Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Vienna, Austria, ou_persistent22              
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
3Max Planck Institute for Biology of Ageing, Cologne, Germany, ou_persistent22              
4Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany, ou_persistent22              
5Institute for Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany, ou_persistent22              

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 Abstract: Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)-containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12-Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum.

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Language(s): eng - English
 Dates: 2020-05-162019-10-092020-07-062020-09-042020-09
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1126/science.aaz7714
BibTex Citekey: sawa-makarska_reconstitution_2020
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Title: Science
  Other : Science
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 369 (6508) Sequence Number: eaaz7714 Start / End Page: - Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1