Evidence map›Paper›PMID 33903617›Full record

ArticleScientific reports2021

Quantitative imaging of membrane contact sites for sterol transfer between endo-lysosomes and mitochondria in living cells.

Alice Dupont Juhl, Christian W Heegaard, Stephan Werner, Gerd Schneider, Kathiresan Krishnan, Douglas F Covey, Daniel Wüstner

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.9field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Organelle contact sites in cancer cells.Cell death & disease · 2026
    Review
  5. Article
  6. Endosomal Mechanisms in Heart Failure Pathophysiology.Current heart failure reports · 2025
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
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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

7 authors at 4 institutions in 3 countries.

Alice Dupont JuhlDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Christian W HeegaardDepartment of Molecular Biology and Genetics, University of Aarhus, 8000, Aarhus C, Denmark.
Stephan WernerDepartment of X-Ray Microscopy, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, 12489, Berlin, Germany.
Gerd SchneiderDepartment of X-Ray Microscopy, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, 12489, Berlin, Germany.
Kathiresan KrishnanDepartment of Developmental Biology, Washington University, St. Louis, MO, 63110, USA.
Douglas F CoveyDepartment of Developmental Biology, Washington University, St. Louis, MO, 63110, USA.
Daniel WüstnerDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark. wuestner@bmb.sdu.dk.
Helmholtz-Zentrum Berlin für Materialien und Energie · DEUniversity of Southern Denmark · DKWashington University in St. Louis · USAarhus University · DK

Funding

Post-lysosomal cholesterol trafficking networksR01HL067773 · NHLBI · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 2002 to 2021
$6.3M
NHLBI NIH HHS R01 HL067773
6 · The paper itself

Abstract

Mitochondria receive cholesterol from late endosomes and lysosomes (LE/LYSs) or from the plasma membrane for production of oxysterols and steroid hormones. This process depends on the endo-lysosomal sterol transfer protein Niemann Pick C2 (NPC2). Using the intrinsically fluorescent cholesterol analog, cholestatrienol, we directly observe sterol transport to mitochondria in fibroblasts upon treating NPC2 deficient human fibroblasts with NPC2 protein. Soft X-ray tomography reveals the ultrastructure of mitochondria and discloses close contact to endosome-like organelles. Using fluorescence microscopy, we localize endo-lysosomes containing NPC2 relative to mitochondria based on the Euclidian distance transform and use statistical inference to show that about 30% of such LE/LYSs are in contact to mitochondria in human fibroblasts. Using Markov Chain Monte Carlo image simulations, we show that interaction between both organelle types, a defining feature of membrane contact sites (MCSs) can give rise to the observed spatial organelle distribution. We devise a protocol to determine the surface fraction of endo-lysosomes in contact with mitochondria and show that this fraction does not depend on functional NPC1 or NPC2 proteins. Finally, we localize MCSs between LE/LYSs containing NPC2 and mitochondria in time-lapse image sequences and show that they either form transiently or remain stable for tens of seconds. Lasting MCSs between endo-lysosomes containing NPC2 and mitochondria move by slow anomalous sub-diffusion, providing location and time for sterol transport between both organelles. Our quantitative imaging strategy will be of high value for characterizing the dynamics and function of MCSs between various organelles in living cells.

Indexed as

Biological Transport, ActiveCell LineFibroblastsHumansLysosomesMaleMicroscopy, FluorescenceMitochondriaMitochondrial MembranesNiemann-Pick C1 ProteinSterolsVesicular Transport ProteinsNiemann-Pick C1 ProteinNPC1 protein, humanNPC2 protein, humanSterolsVesicular Transport Proteins

Identifiers

PMID33903617
PMCPMC8076251
OpenAlexW3159402091

What OpenQuestion holds

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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.