Evidence map›Paper›PMID 39774270›Full record

ArticleNature cell biology2025

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy.

Mariya Licheva, Jeremy Pflaum, Riccardo Babic, Hector Mancilla, Jana Elsässer, Emily Boyle, David M Hollenstein, Jorge Jimenez-Niebla, Jonas Pleyer, Mio Heinrich and 11 more

Erratum issuedAbstract read
In one paragraph

Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. The Human Autophagy Core Complexes.Annual review of biochemistry · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Core principles of autophagy initiation mechanisms.Nature structural & molecular biology · 2026
    Review
  11. Role of autophagy in antiviral innate immunity.Cellular & molecular biology letters · 2026
    Review
  12. Article
  13. Review
  14. Autophagy in the liver.Autophagy reports · 2026
    Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. The autophagy-specific exocyst subcomplex contributes to phagophore assembly site integrity by promoting phagophore expansion.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Mariya Licheva *Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-7722-7340
Jeremy Pflaum *Mechanisms of Cellular Quality Control, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID http://orcid.org/0009-0000-4878-8229
Riccardo Babic *Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0177-2251
Hector Mancilla *Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-4929-3388
Jana ElsässerInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-9786-6035
Emily BoyleMechanisms of Cellular Quality Control, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0001-8803-3939
David M HollensteinDepartment for Biochemistry and Cell Biology, University of Vienna, Center for Molecular Biology, Vienna Biocenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0002-1977-1556
Jorge Jimenez-NieblaInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0009-0008-1643-1688
Jonas PleyerFreiburg Center for Data Analysis and Modelling (FDM), University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0009-0001-0613-7978
Mio HeinrichFreiburg Center for Data Analysis and Modelling (FDM), University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0009-0009-4267-7195
Franz-Georg WielandFreiburg Center for Data Analysis and Modelling (FDM), University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-5629-8622
Joachim BrenneisenInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0009-0002-3622-6434
Christopher EickhorstInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-1545-4016
Johann BrennerMechanisms of Cellular Quality Control, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0003-1306-3564
Shan JiangMechanisms of Cellular Quality Control, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-1540-8506
Markus HartlDepartment for Biochemistry and Cell Biology, University of Vienna, Center for Molecular Biology, Vienna Biocenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0002-4970-7336
Sonja WelschCentral Electron Microscopy Facility, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-6049-6664
Carola HunteInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0826-3986
Jens TimmerFreiburg Center for Data Analysis and Modelling (FDM), University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-4517-1383
Florian WilflingMechanisms of Cellular Quality Control, Max Planck Institute of Biophysics, Frankfurt am Main, Germany. florian.wilfling@biophys.mpg.de.ORCID http://orcid.org/0000-0002-6559-7261
Claudine KraftInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany. kraft@biochemie.uni-freiburg.de.ORCID http://orcid.org/0000-0002-3324-4701

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) 259130777Deutsche Forschungsgemeinschaft (German Research Foundation) 390939984Deutsche Forschungsgemeinschaft (German Research Foundation) 403222702Deutsche Forschungsgemeinschaft (German Research Foundation) 409673687Deutsche Forschungsgemeinschaft (German Research Foundation) 423813989Deutsche Forschungsgemeinschaft (German Research Foundation) 450216812EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101041982EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 769065
6 · The paper itself

Abstract

Autophagy is a key cellular quality control mechanism. Nutrient stress triggers bulk autophagy, which nonselectively degrades cytoplasmic material upon formation and liquid-liquid phase separation of the autophagy-related gene 1 (Atg1) complex. In contrast, selective autophagy eliminates protein aggregates, damaged organelles and other cargoes that are targeted by an autophagy receptor. Phase separation of cargo has been observed, but its regulation and impact on selective autophagy are poorly understood. Here, we find that key autophagy biogenesis factors phase separate into initiation hubs at cargo surfaces in yeast, subsequently maturing into sites that drive phagophore nucleation. This phase separation is dependent on multivalent, low-affinity interactions between autophagy receptors and cargo, creating a dynamic cargo surface. Notably, high-affinity interactions between autophagy receptors and cargo complexes block initiation hub formation and autophagy progression. Using these principles, we converted the mammalian reovirus nonstructural protein µNS, which accumulates as particles in the yeast cytoplasm that are not degraded, into a neo-cargo that is degraded by selective autophagy. We show that initiation hubs also form on the surface of different cargoes in human cells and are key to establish the connection to the endoplasmic reticulum, where the phagophore assembly site is formed to initiate phagophore biogenesis. Overall, our findings suggest that regulated phase separation underscores the initiation of both bulk and selective autophagy in evolutionarily diverse organisms.

Indexed as

AutophagyAutophagy-Related ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAnimalsHumansPhase SeparationProtein KinasesATG1 protein, S cerevisiaeAutophagy-Related ProteinsProtein KinasesSaccharomyces cerevisiae Proteins

Identifiers

PMID39774270
PMCPMC11821514

What OpenQuestion holds

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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.