Evidence map›Paper›PMID 31537798›Full record

ArticleNature communications2019

NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress.

D Höglinger, T Burgoyne, E Sanchez-Heras, P Hartwig, A Colaco, J Newton, C E Futter, S Spiegel, F M Platt, E R Eden

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed, 2 pooled it
17.9field-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

184 citing papers in PubMed, 2 syntheses or guidelines pooled it, 275 citations in OpenAlex.

  1. Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024
    Pooled it
  2. Pooled it
  3. Review
  4. Article
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  7. Article
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  9. Article
  10. Review
  11. Review
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  13. Organelle contact sites in cancer cells.Cell death & disease · 2026
    Review
  14. Article
  15. Article
  16. Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026
    Review
  17. Article
  18. Article
  19. Review
  20. Review

124 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

10 authors at 6 institutions in 4 countries.

D HöglingerDepartment of Pharmacology, University of Oxford, Oxford, UK.
T BurgoyneUCL Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0002-8428-720X
E Sanchez-HerasUCL Institute of Ophthalmology, London, UK.
P HartwigHeidelberg University Biochemistry Center (BZH), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-9344-7714
A ColacoDepartment of Pharmacology, University of Oxford, Oxford, UK.
J NewtonDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
C E FutterUCL Institute of Ophthalmology, London, UK.
S SpiegelDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
F M PlattDepartment of Pharmacology, University of Oxford, Oxford, UK.
E R EdenUCL Institute of Ophthalmology, London, UK. e.eden@ucl.ac.uk.ORCID http://orcid.org/0000-0001-9352-5532
Heidelberg University · DEUniversity College London · GBUniversity of Oxford · GBVirginia Commonwealth University · USEnergy Institute · GBRoyal Brompton Hospital · GB

Funding

SPHINGOSINE AS A MODULATOR OF CELLULAR PROLIFERATIONR01GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1990 to 2023
$3.8M
New approach for cholesterol and sphingolipid reduction in Niemann-Pick C1 diseaseK99HD096117 · NICHD · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEWTON, JASON CHARLES · 2018 to 2019
$248k
Biotechnology and Biological Sciences Research Council BB/S009566/1Medical Research Council G0801878Medical Research Council MR/P010091/1NICHD NIH HHS K99 HD096117NIGMS NIH HHS R01 GM043880NINDS NIH HHS L40 NS108774Wellcome Trust 202834/Z/16/Z
6 · The paper itself

Abstract

Transport of dietary cholesterol from endocytic organelles to the endoplasmic reticulum (ER) is essential for cholesterol homoeostasis, but the mechanism and regulation of this transport remains poorly defined. Membrane contact sites (MCS), microdomains of close membrane apposition, are gaining attention as important platforms for non-vesicular, inter-organellar communication. Here we investigate the impact of ER-endocytic organelle MCS on cholesterol transport. We report a role for Niemann-Pick type C protein 1 (NPC1) in tethering ER-endocytic organelle MCS where it interacts with the ER-localised sterol transport protein Gramd1b to regulate cholesterol egress. We show that artificially tethering MCS rescues the cholesterol accumulation that characterises NPC1-deficient cells, consistent with direct lysosome to ER cholesterol transport across MCS. Finally, we identify an expanded population of lysosome-mitochondria MCS in cells depleted of NPC1 or Gramd1b that is dependent on the late endosomal sterol-binding protein STARD3, likely underlying the mitochondrial cholesterol accumulation in NPC1-deficient cells.

Indexed as

AnimalsBiological TransportCarrier ProteinsCell Line, TumorCHO CellsCholesterolCricetinaeCricetulusEndoplasmic ReticulumHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMembrane ProteinsMitochondriaNiemann-Pick C1 ProteinCarrier ProteinsCholesterolGRAMD1B protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsNiemann-Pick C1 ProteinNPC1 protein, humanRNA, Small InterferingSTARD3 protein, human

Identifiers

PMID31537798
PMCPMC6753064
OpenAlexW2973648545

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.