Evidence map›Paper›PMID 31917335›Full record

ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2020

Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis.

David B Iaea, Zachary R Spahr, Rajesh K Singh, Robin B Chan, Bowen Zhou, Rohan Bareja, Olivier Elemento, Gilbert Di Paolo, Xiaoxue Zhang, Frederick R Maxfield

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Sleep loss induces cholesterol-associated myelin dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.Frontiers in cell and developmental biology · 2022
    Review
  12. Article
  13. Review
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 2 institutions in 1 country.

David B IaeaDepartment of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA; Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center Tri-Institutional Chemical Biology Program, New York, NY 10065, USA.
Zachary R SpahrDepartment of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
Rajesh K SinghDepartment of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
Robin B ChanPathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Bowen ZhouPathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Rohan BarejaInstitute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
Olivier ElementoInstitute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
Gilbert Di PaoloPathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Xiaoxue ZhangDepartment of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
Frederick R MaxfieldDepartment of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA; Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center Tri-Institutional Chemical Biology Program, New York, NY 10065, USA. Electronic address: frmaxfie@med.cornell.edu.
Cornell University · USColumbia University Irving Medical Center · US

Funding

Role of phospholipids in membrane traffic at the synapseR01NS056049 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIEM, RONALD K. · 2006 to 2016
$3.7M
The identification and validation of mechanisms and biomarkers for relapse in diffuse large B-cell lymphoma (Administrative Supplement)R01CA194547 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ELEMENTO, OLIVIER, TAM, WAYNE · 2015 to 2019
$2.6M
Intracellular Cholesterol TransportR01GM123462 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI MAXFIELD, FREDERICK R. · 2018 to 2021
$1.4M
Structure-function studies of the sterol transport protein, STARD4.F31DK104631 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI IAEA, DAVID BURTON · 2015 to 2016
$69k
NCI NIH HHS R01 CA194547NIDDK NIH HHS F31 DK104631NIGMS NIH HHS R01 GM123462NINDS NIH HHS R01 NS056049
6 · The paper itself

Abstract

STARD4, a member of the evolutionarily conserved START gene family, is a soluble sterol transport protein implicated in cholesterol sensing and maintenance of cellular homeostasis. STARD4 is widely expressed and has been shown to transfer sterol between liposomes as well as organelles in cells. However, STARD4 knockout mice lack an obvious phenotype, so the overall role of STARD4 is unclear. To model long term depletion of STARD4 in cells, we use short hairpin RNA technology to stably decrease STARD4 expression in human U2OS osteosarcoma cells (STARD4-KD). We show that STARD4-KD cells display increased total cholesterol, slower cholesterol trafficking between the plasma membrane and the endocytic recycling compartment, and increased plasma membrane fluidity. These effects can all be rescued by transient expression of a short hairpin RNA-resistant STARD4 construct. Some of the cholesterol increase was due to excess storage in late endosomes or lysosomes. To understand the effects of reduced STARD4, we carried out transcriptional and lipidomic profiling of control and STARD4-KD cells. Reduction of STARD4 activates compensatory mechanisms that alter membrane composition and lipid homeostasis. Based on these observations, we propose that STARD4 functions as a critical sterol transport protein involved in sterol sensing and maintaining lipid homeostasis.

Indexed as

Lipid MetabolismBiological TransportCell Line, TumorCell MembraneCholesterolEndocytosisHumansLipidomicsMembrane Transport ProteinsRNA InterferenceRNA, Small InterferingCholesterolMembrane Transport ProteinsRNA, Small InterferingSTARD4 protein, humanCholesterolComputational biologyGene expressionLipidomicsLipidsMembrane lipids

Identifiers

PMID31917335
PMCPMC6996790
OpenAlexW2999323012

What OpenQuestion holds

Textmetadata
LicenceTDM
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.