Evidence map›Paper›PMID 30578317›Full record

ArticleJournal of cell science2019

The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis.

Norbert Volkmar, Maria-Laetitia Thezenas, Sharon M Louie, Szymon Juszkiewicz, Daniel K Nomura, Ramanujan S Hegde, Benedikt M Kessler, John C Christianson

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
5.6field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

  1. Pooled it
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  7. Article
  8. Review
  9. Time-resolved photocatalytic proximity labeling uncovers ER proteome dynamics underlying UPR-to-apoptosis transition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. EMC rectifies the topology of multipass membrane proteins.Nature structural & molecular biology · 2024
    Article
  19. Article
  20. Article

5 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

8 authors at 4 institutions in 2 countries.

Norbert VolkmarLudwig Institute for Cancer Research, University of Oxford, ORCRB, Headington, Oxford, OX3 7DQ, UK.ORCID 0000-0003-0766-5606
Maria-Laetitia ThezenasTarget Discovery Institute (TDI) Mass Spectrometry Laboratory, Nuffield Department of Medicine, University of Oxford, Headington, Oxford, OX3 7DQ, UK.
Sharon M LouieDept. of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, University of California-Berkeley, Berkeley, CA, 94720, USA.
Szymon JuszkiewiczMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.ORCID 0000-0002-3361-7264
Daniel K NomuraDept. of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, University of California-Berkeley, Berkeley, CA, 94720, USA.ORCID 0000-0003-1614-8360
Ramanujan S HegdeMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.ORCID 0000-0001-8338-852X
Benedikt M KesslerTarget Discovery Institute (TDI) Mass Spectrometry Laboratory, Nuffield Department of Medicine, University of Oxford, Headington, Oxford, OX3 7DQ, UK.ORCID 0000-0002-8160-2446
John C ChristiansonLudwig Institute for Cancer Research, University of Oxford, ORCRB, Headington, Oxford, OX3 7DQ, UK john.christianson@ndorms.ox.ac.uk.ORCID 0000-0002-0474-1207
MRC Laboratory of Molecular Biology · GBNuffield Orthopaedic Centre · GBUniversity of California, Berkeley · USUniversity of Oxford · GB

Funding

Annotating the Role of Dysregulated Inositol Phosphate Metabolism in Malignant CaR01CA172667 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI NOMURA, DANIEL · 2013 to 2017
$1.7M
Medical Research Council MC_UP_A022_1007Medical Research Council MR/L001209/1NCI NIH HHS R01 CA172667Wellcome TrustWellcome Trust 097813/Z/11/Z
6 · The paper itself

Abstract

The eukaryotic endoplasmic reticulum (ER) membrane contains essential complexes that oversee protein biogenesis and lipid metabolism, impacting nearly all aspects of cell physiology. The ER membrane protein complex (EMC) is a newly described transmembrane domain (TMD) insertase linked with various phenotypes, but whose clients and cellular responsibilities remain incompletely understood. We report that EMC deficiency limits the cellular boundaries defining cholesterol tolerance, reflected by diminished viability with limiting or excessive extracellular cholesterol. Lipidomic and proteomic analyses revealed defective biogenesis and concomitant loss of the TMD-containing ER-resident enzymes sterol-O-acyltransferase 1 (SOAT1) and squalene synthase (SQS, also known as FDFT1), which serve strategic roles in the adaptation of cells to changes in cholesterol availability. Insertion of the weakly hydrophobic tail-anchor (TA) of SQS into the ER membrane by the EMC ensures sufficient flux through the sterol biosynthetic pathway while biogenesis of polytopic SOAT1 promoted by the EMC provides cells with the ability to store free cholesterol as inert cholesteryl esters. By facilitating insertion of TMDs that permit essential mammalian sterol-regulating enzymes to mature accurately, the EMC is an important biogenic determinant of cellular robustness to fluctuations in cholesterol availability.This article has an associated First Person interview with the first author of the paper.

Indexed as

Cell Line, TumorCholesterolEndoplasmic ReticulumFarnesyl-Diphosphate FarnesyltransferaseHumansIntracellular MembranesMultienzyme ComplexesSterol O-AcyltransferaseCholesterolFarnesyl-Diphosphate FarnesyltransferaseMultienzyme ComplexesSterol O-Acyltransferasesterol O-acyltransferase 1Cholesterol homeostasisEMCEndoplasmic reticulumSOAT1Squalene synthase

Identifiers

PMID30578317
PMCPMC6362398
OpenAlexW2906243785

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.