Evidence map›Paper›PMID 38895340›Full record

ArticlebioRxiv : the preprint server for biology2024

CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.

Alyssa J Mathiowetz, Emily S Meymand, Kirandeep K Deol, Güneş Parlakgül, Mike Lange, Stephany P Pang, Melissa A Roberts, Emily F Torres, Danielle M Jorgens, Reena Zalpuri and 11 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Alyssa J MathiowetzDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Emily S MeymandDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Kirandeep K DeolDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Güneş ParlakgülDepartment of NutriYonal Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Mike LangeDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Stephany P PangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Melissa A RobertsDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Emily F TorresDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Danielle M JorgensElectron Microscope Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
Reena ZalpuriElectron Microscope Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
Misun KangElectron Microscope Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
Casadora BooneDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Yaohuan ZhangDepartment of NutriYonal Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
David W MorgensDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Emily TsoMerck & Co., Inc., South San Francisco, CA 94080, USA.
Yingjiang ZhouMerck & Co., Inc., South San Francisco, CA 94080, USA.
Saswata TalukdarMerck & Co., Inc., South San Francisco, CA 94080, USA.
Tim P LevineUniversity College London InsYtute of Ophthalmology, Bath Street London, EC1V 9EL, UK.
Gregory KuDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Ana Paula ArrudaDepartment of NutriYonal Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
James A OlzmannDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-7751-8316

Funding

Molecular Mechanisms of Lipid Droplet BiogenesisR01GM112948 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI OLZMANN, JAMES A · 2015 to 2024
$3.1M
PREP @ UC BerkeleyR25GM140276 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI GIAN GARRIGA, Julia Schaletzky · 2022 to 2026
$1.9M
ICP-QQQS10OD030258 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI JORGENS, DANIELLE MARY · 2021 to 2021
$1.6M
Lipid droplet regulation and proteome dynamicsR01DK128099 · NIDDK · UNIVERSITY OF CALIFORNIA BERKELEY · PI OLZMANN, JAMES A · 2021 to 2025
$1.6M
The role of hepatic Endoplasmic Reticulum architecture in metabolic homeostasis and diseaseR01DK140367 · NIDDK · UNIVERSITY OF CALIFORNIA BERKELEY · PI Ana Paula Arruda · 2024 to 2026
$1.2M
Defining the role of ubiquitination in the regulation of lipid dropletsR00DK095921 · NIDDK · UNIVERSITY OF CALIFORNIA BERKELEY · PI OLZMANN, JAMES A · 2013 to 2015
$843k
Acquisition of an Orbitrap MSS10OD010645 · OD · UNIVERSITY OF MASSACHUSETTS AMHERST · PI EYLES, STEPHEN J. · 2013 to 2013
$600k
NIDDK NIH HHS R00 DK095921NIDDK NIH HHS R01 DK128099NIDDK NIH HHS R01 DK140367NIGMS NIH HHS R01 GM112948NIGMS NIH HHS R25 GM140276NIH HHS S10 OD010645NIH HHS S10 OD030258
6 · The paper itself

Abstract

Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte lipid droplets (LDs) (i.e., hepatic steatosis). Our understanding of the mechanisms that govern the channeling of hepatocyte neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series of CRISPR-Cas9 screens under different metabolic states to uncover mechanisms of hepatic neutral lipid flux. Clustering of chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as a critical regulator of neutral lipid storage and secretion. Loss of CLCC1 resulted in the buildup of large LDs in hepatoma cells and knockout in mice caused liver steatosis. Remarkably, the LDs are in the lumen of the ER and exhibit properties of lipoproteins, indicating a profound shift in neutral lipid flux. Finally, remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1p and Brr6p, factors that promote the fusion of the inner and outer nuclear envelopes during nuclear pore complex assembly. Loss of CLCC1 lead to extensive nuclear membrane herniations, consistent with impaired nuclear pore complex assembly. Thus, we identify CLCC1 as the human Brl1p/Brr6p homolog and propose that CLCC1-mediated membrane remodeling promotes hepatic neutral lipid flux and nuclear pore complex assembly.

Identifiers

PMID38895340
PMCPMC11185754

What OpenQuestion holds

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Registered trials

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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.