The autophagic membrane tether ATG2A transfers lipids between membranes

  1. Shintaro Maeda
  2. Chinatsu Otomo
  3. Takanori Otomo  Is a corresponding author
  1. The Scripps Research Institute, United States

Abstract

An enigmatic step in de novo formation of the autophagosome membrane compartment is the expansion of the precursor membrane phagophore, which requires the acquisition of lipids to serve as building blocks. Autophagy-related 2 (ATG2), the rod-shaped protein that tethers phosphatidylinositol 3-phosphate (PI3P)-enriched phagophores to the endoplasmic reticulum (ER), is suggested to be essential for phagophore expansion, but the underlying mechanism remains unclear. Here, we demonstrate that human ATG2A is a lipid-transferring protein. ATG2A can extract lipids from membrane vesicles and unload them to other vesicles. Lipid transfer by ATG2A is more efficient between tethered vesicles than between untethered vesicles. The PI3P effectors WIPI4 and WIPI1 associate ATG2A stably to PI3P-containing vesicles, thereby facilitating ATG2A-mediated tethering and lipid transfer between PI3P-containing vesicles and PI3P-free vesicles. Based on these results, we propose that ATG2-mediated transfer of lipids from the ER to the phagophore enables phagophore expansion.

Data availability

All data generated and analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Shintaro Maeda

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chinatsu Otomo

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Takanori Otomo

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    For correspondence
    totomo@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3589-238X

Funding

National Institute of General Medical Sciences (R01GM092740)

  • Takanori Otomo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Pedro Carvalho, University of Oxford, United Kingdom

Version history

  1. Received: February 4, 2019
  2. Accepted: July 2, 2019
  3. Accepted Manuscript published: July 4, 2019 (version 1)
  4. Version of Record published: July 12, 2019 (version 2)

Copyright

© 2019, Maeda et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shintaro Maeda
  2. Chinatsu Otomo
  3. Takanori Otomo
(2019)
The autophagic membrane tether ATG2A transfers lipids between membranes
eLife 8:e45777.
https://doi.org/10.7554/eLife.45777

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