Evidence map›Paper›PMID 36516251›Full record

ArticleScience advances2022

Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery.

Liv E Jensen, Shanlin Rao, Martina Schuschnig, A King Cada, Sascha Martens, Gerhard Hummer, James H Hurley

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
6.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. The Human Autophagy Core Complexes.Annual review of biochemistry · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. ATG16L1 induces the formation of phagophore-like membrane cups.Nature structural & molecular biology · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Liv E JensenDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0003-1492-1743
Shanlin RaoAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0003-4892-5523
Martina SchuschnigDepartment of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Vienna BioCenter, Vienna, Austria.ORCID 0000-0002-8926-6432
A King CadaDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0002-9284-0941
Sascha MartensAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0003-3786-8199
Gerhard HummerAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0001-7768-746X
James H HurleyDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-5054-5445
QB3 · USUniversity of Vienna · ATGoethe University Frankfurt · DEMax Planck Institute of Biophysics · DE

Funding

The Autophagy Initiation ComplexesR01GM111730 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H · 2014 to 2021
$2.2M
Reverse-Topology Mechanism of ESCRTs DuringHIV-1 Viral ReleaseF31AI150312 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI CADA, ABRAHAM KING · 2019 to 2021
$125k
Austrian Science Fund FWF W 1261NIAID NIH HHS F31 AI150312NIGMS NIH HHS R01 GM111730
6 · The paper itself

Abstract

How the highly curved phagophore membrane is stabilized during autophagy initiation is a major open question in autophagosome biogenesis. Here, we use in vitro reconstitution on membrane nanotubes and molecular dynamics simulations to investigate how core autophagy proteins in the LC3 (Microtubule-associated proteins 1A/1B light chain 3) lipidation cascade interact with curved membranes, providing insight into their possible roles in regulating membrane shape during autophagosome biogenesis. ATG12(Autophagy-related 12)-ATG5-ATG16L1 was up to 100-fold enriched on highly curved nanotubes relative to flat membranes. At high surface density, ATG12-ATG5-ATG16L1 binding increased the curvature of the nanotubes. While WIPI2 (WD repeat domain phosphoinositide-interacting protein 2) binding directs membrane recruitment, the amphipathic helix α2 of ATG16L1 is responsible for curvature sensitivity. Molecular dynamics simulations revealed that helix α2 of ATG16L1 inserts shallowly into the membrane, explaining its curvature-sensitive binding to the membrane. These observations show how the binding of the ATG12-ATG5-ATG16L1 complex to the early phagophore rim could stabilize membrane curvature and facilitate autophagosome growth.

Identifiers

PMID36516251
PMCPMC9750143
OpenAlexW4311441084

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.