Evidence map›Paper›PMID 35653304›Full record

ArticleMolecular biology of the cell2022

BORC-ARL8-HOPS ensemble is required for lysosomal cholesterol egress through NPC2.

Jacob Anderson, Gerard Walker, Jing Pu

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Niemann-Pick Disease Type C (NPDC) by Mutation ofAntioxidants (Basel, Switzerland) · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
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

3 authors at 2 institutions in 1 country.

Jacob AndersonDepartment of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131.
Gerard WalkerNeurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Jing PuDepartment of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131.
University of New Mexico · USNational Institutes of Health · US

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI VOJO P DERETIC · 2017 to 2026
$24.9M
Lysosome‐Lipid Droplet Interactions in Fatty Acid MetabolismR35GM147419 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Jing Pu · 2022 to 2026
$1.9M
NCI NIH HHS P30 CA118100NIGMS NIH HHS P20 GM121176NIGMS NIH HHS R35 GM147419
6 · The paper itself

Abstract

Lysosomes receive extracellular and intracellular cholesterol and redistribute it throughout the cell. Cholesterol egress from lysosomes is critical for cholesterol homeostasis, and its failure underlies the pathogenesis of genetic disorders such as Niemann-Pick C (NPC) disease. Here we report that the BLOC one-related complex (BORC)-ARL8-homotypic fusion and protein sorting (HOPS) ensemble is required for egress of free cholesterol from lysosomes and for storage of esterified cholesterol in lipid droplets. Depletion of BORC, ARL8, or HOPS does not alter the localization of the lysosomal transmembrane cholesterol transporter NPC1 to degradative compartments but decreases the association of the luminal transporter NPC2 and increases NPC2 secretion. BORC-ARL8-HOPS depletion also increases lysosomal degradation of cation-independent (CI)-mannose 6-phosphate (M6P) receptor (MPR), which normally sorts NPC2 to the endosomal-lysosomal system and then is recycled to the trans-Golgi network. These defects likely result from impaired HOPS-dependent fusion of endosomal-lysosomal organelles and an uncharacterized function of HOPS in CI-MPR recycling. Our study demonstrates that the BORC-ARL8-HOPS ensemble is required for cholesterol egress from lysosomes by enabling CI-MPR-dependent trafficking of NPC2 to the endosomal-lysosomal system.

Indexed as

LysosomesVesicular Transport ProteinsCholesterolEndosomesProtein TransportCholesterolVesicular Transport Proteins

Identifiers

PMID35653304
PMCPMC9582633
OpenAlexW4282931532

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.