Evidence map›Paper›PMID 25686604›Full record

ArticleNature2015

ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.

Jiajie Diao, Rong Liu, Yueguang Rong, Minglei Zhao, Jing Zhang, Ying Lai, Qiangjun Zhou, Livia M Wilz, Jianxu Li, Sandro Vivona and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 337 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
337citing papers in PubMed, 1 pooled it
40.3field-weighted citation impact, top 1% 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

337 citing papers in PubMed, 1 synthesis or guideline pooled it, 557 citations in OpenAlex.

  1. Guideline
  2. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026
    Review
  10. Article
  11. Article
  12. VAMP8 function reveals tight linkage between endocytic recycling and endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025
    Review
  19. NADCells · 2025
    Review
  20. Review

277 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 1 country.

Jiajie Diao1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Rong Liu1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [3] College of Food Science &Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Yueguang Rong1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Minglei Zhao1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Jing Zhang1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Ying Lai1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Qiangjun Zhou1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Livia M WilzDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
Jianxu LiDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
Sandro Vivona1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Richard A Pfuetzner1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Axel T Brunger1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Qing Zhong1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Stanford University · USThe University of Texas Southwestern Medical Center · USUniversity of California, Berkeley · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
THE MOLECULAR BASIS OF CELL FUNCTIONT32GM007232 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BILDER, DAVID, UNAL, ELCIN · 1985 to 2022
$36.4M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
STRUCTURE OF PROTEINS INVOLVED IN SYNAPTIC EXOCYTOSISR01MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2000 to 2025
$4.7M
Single molecule studies of SNARE-induced vesicle fusionR37MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2011 to 2020
$4.7M
Molecular Mechanism of Mule in DNA Damage Response and TumorigenesisR01CA133228 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHONG, QING · 2009 to 2013
$1.5M
Howard Hughes Medical InstituteNCI NIH HHS 5P30CA142543NCI NIH HHS P30 CA142543NCI NIH HHS R01 CA133228NIGMS NIH HHS P41 GM103403NIGMS NIH HHS T32 GM007232NIMH NIH HHS R01 R37-MH63105NIMH NIH HHS R37 MH063105
6 · The paper itself

Abstract

Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.

Indexed as

AutophagyMembrane FusionAdaptor Proteins, Vesicular TransportAutophagy-Related ProteinsEndosomesHEK293 CellsHeLa CellsHumansLysosomesPhagosomesProtein BindingProtein MultimerizationProtein Structure, TertiaryQa-SNARE ProteinsQb-SNARE ProteinsQc-SNARE ProteinsAdaptor Proteins, Vesicular TransportATG14 protein, humanAutophagy-Related ProteinsQa-SNARE ProteinsQb-SNARE ProteinsQc-SNARE ProteinsR-SNARE ProteinsSNAP29 protein, humanSNARE ProteinsSTX17 protein, humanVAMP8 protein, human

Identifiers

PMID25686604
PMCPMC4442024
OpenAlexW2009490810

What OpenQuestion holds

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Read underepoch 390

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.