Evidence map›Paper›PMID 34645799›Full record

ArticleCell death & disease2021

Prefused lysosomes cluster on autophagosomes regulated by VAMP8.

Qixin Chen, Mingang Hao, Lei Wang, Linsen Li, Yang Chen, Xintian Shao, Zhiqi Tian, Richard A Pfuetzner, Qing Zhong, Axel T Brunger and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
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  5. 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
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  7. Review
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  12. A Small-Molecule Drug for the Self-Checking of Mitophagy.Angewandte Chemie (International ed. in English) · 2025
    Article
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  14. Review
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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

12 authors at 5 institutions in 2 countries.

Qixin Chen *Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Mingang Hao *Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Lei Wang *Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Linsen LiState Key Lab of Animal Nutrition, China Agricultural University, Beijing, 100193, China.
Yang ChenDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Xintian ShaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Zhiqi TianDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Richard A PfuetznerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, 94305, CA, USA.
Qing ZhongKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
Axel T BrungerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, 94305, CA, USA.
Jun-Lin GuanDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. guanjl@ucmail.uc.edu.ORCID 0000-0001-8720-8338
Jiajie DiaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. jiajie.diao@uc.edu.ORCID 0000-0003-4288-3203
University of Cincinnati Medical Center · USHoward Hughes Medical Institute · USChina Agricultural University · CNShanghai Jiao Tong University · CNUniversity of Cincinnati · US

Funding

Regulation of Neural Stem Cells and Neurogenesis by Autophagy GenesR01NS094144 · NINDS · UNIVERSITY OF CINCINNATI · PI GUAN, JUN-LIN · 2015 to 2024
$3.6M
Mechanisms of FIP200 regulation of breast cancer through its autophagy and non-autophagy functionsR01CA211066 · NCI · UNIVERSITY OF CINCINNATI · PI JUN-LIN GUAN · 2017 to 2026
$3.4M
The crosstalk of organelles involved in autophagosome biogenesisR35GM128837 · NIGMS · UNIVERSITY OF CINCINNATI · PI Jiajie Diao · 2018 to 2026
$3.3M
Biochemical Dissection and Reconstitution of Autophagic Membrane FusionR01GM116908 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ZHONG, QING · 2015 to 2018
$1.3M
NCI NIH HHS R01 CA211066NIGMS NIH HHS R01 GM116908NIGMS NIH HHS R35 GM128837NINDS NIH HHS R01 NS094144
6 · The paper itself

Abstract

Lysosome-autophagosome fusion is critical to autophagosome maturation. Although several proteins that regulate this fusion process have been identified, the prefusion architecture and its regulation remain unclear. Herein, we show that upon stimulation, multiple lysosomes form clusters around individual autophagosomes, setting the stage for membrane fusion. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein on lysosomes-vesicle-associated membrane protein 8 (VAMP8)-plays an important role in forming this prefusion state of lysosomal clusters. To study the potential role of phosphorylation on spontaneous fusion, we investigated the effect of phosphorylation of C-terminal residues of VAMP8. Using a phosphorylation mimic, we observed a decrease of fusion in an ensemble lipid mixing assay and an increase of unfused lysosomes associated with autophagosomes. These results suggest that phosphorylation not only reduces spontaneous fusion for minimizing autophagic flux under normal conditions, but also preassembles multiple lysosomes to increase the fusion probability for resuming autophagy upon stimulation. VAMP8 phosphorylation may thus play an important role in chemotherapy drug resistance by influencing autophagosome maturation.

Indexed as

Membrane FusionAutophagosomesCarbonyl Cyanide m-Chlorophenyl HydrazoneDrug Resistance, NeoplasmHeLa CellsHumansLysosomesPhosphorylationR-SNARE ProteinsSNARE ProteinsTemozolomideCarbonyl Cyanide m-Chlorophenyl HydrazoneR-SNARE ProteinsSNARE ProteinsTemozolomideVAMP8 protein, human

Identifiers

PMID34645799
PMCPMC8514493
OpenAlexW3207406928

What OpenQuestion holds

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LicenceCC BY
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.