Evidence map›Paper›PMID 41544616›Full record

ArticleCell chemical biology2026

1-deoxysphingolipids dysregulate membrane properties and cargo trafficking in the early secretory pathway.

Yi-Ting Tsai, Nicolas-Frédéric Lipp, Olivia Seidel, Riya Varma, Aurelie Laguerre, Kristina Solorio-Kirpichyan, Adrian M Wong, Roberto J Brea, Grace H McGregor, Thekla Cordes and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Yi-Ting TsaiDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Nicolas-Frédéric LippDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Olivia SeidelDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Riya VarmaDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Aurelie LaguerreDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute of Biological Studies, La Jolla, CA 92037, USA.
Kristina Solorio-KirpichyanDepartment of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Adrian M WongDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Roberto J BreaDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA; CICA - Centro Interdisciplinar de Química e Bioloxía e Departamento de Química, Facultade de Ciencias, Universidade da Coruña, Rúa As Carballeiras, 15701 A Coruña, Spain.
Grace H McGregorDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute of Biological Studies, La Jolla, CA 92037, USA.
Thekla CordesDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute of Biological Studies, La Jolla, CA 92037, USA.
Neal K DevarajDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA.
Lars KuerschnerLife & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
Sonya NealDepartment of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Christian M MetalloDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute of Biological Studies, La Jolla, CA 92037, USA.
Itay BudinDepartment of Biochemistry & Molecular Biophysics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: ibudin@ucsd.edu.

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Lipidic drivers of organelle function and dysregulationR35GM142960 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Itay Budin · 2021 to 2026
$4.3M
Molecular Biophysics Training Grant at UC San DiegoT32GM139795 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Galia Debelouchina, ELIZABETH A. KOMIVES · 2021 to 2026
$3.0M
The Discovery of Molecules and Mechanisms of the Rhomboid SuperfamilyR35GM133565 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sonya Elina Neal · 2019 to 2026
$2.9M
Illuminating cellular dark matter through the development of novel chemical toolsR35GM141939 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVARAJ, NEAL KRISHNA · 2021 to 2025
$2.2M
Non-essential amino acids and sphingolipid diversity in cancer progressionR01CA234245 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI METALLO, CHRISTIAN MICHAEL · 2019 to 2023
$1.9M
Chemistry-Biology Interfaces at UCSDT32GM146648 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael D. Burkart, Alexis C. Komor · 2022 to 2026
$876k
NCI NIH HHS R01 CA234245NIGMS NIH HHS K12 GM068524NIGMS NIH HHS R35 GM133565NIGMS NIH HHS R35 GM141939NIGMS NIH HHS R35 GM142960NIGMS NIH HHS T32 GM139795NIGMS NIH HHS T32 GM146648
6 · The paper itself

Abstract

1-Deoxysphingolipids are non-canonical sphingolipids linked to several diseases, yet their cellular effects are poorly understood. Here, we utilize lipid chemical biology approaches to investigate the role of 1-deoxysphingolipid metabolism on the properties and functions of secretory membranes. We applied organelle-specific bioorthogonal labeling to visualize the subcellular distribution of metabolically tagged sphingolipids. We observed that 1-deoxysphingolipids are retained in the endoplasmic reticulum (ER) and specifically in ER exit sites (ERESs), suggesting that they do not efficiently sort into vesicular carriers. Cell lines expressing disease-associated variants of serine palmitoyl-CoA transferase accumulated 1-deoxysphingolipids, which were accompanied by a reduction in ER membrane fluidity and enlargement of ERES. We found that the rates of membrane protein release from the ER were altered in response to 1-deoxysphingolipid metabolism in a manner dependent on the protein's affinity for ordered or disordered membranes. The dysregulation of sphingolipid metabolism can thus alter secretory membrane properties and affect protein trafficking.

Indexed as

Endoplasmic ReticulumSecretory PathwaySphingolipidsAnimalsCell MembraneHumansProtein TransportSerine C-Palmitoyltransferase1-deoxysphingolipidSerine C-PalmitoyltransferaseSphingolipidsceramidesendoplasmic reticulummembrane fluiditysphingolipidstrafficking

Identifiers

PMID41544616
PMCPMC12818558

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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.