Evidence map›Paper›PMID 40326774›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2025

Reduced Palmitoylation of SQSTM1/p62 in Huntington Disease Is Associated With Impaired Autophagy.

F Abrar, M C Davies, Y Alshehabi, A Kumar, A Dang, Y T N Nguyen, J Collins, N S Caron, J S Choudhary, S S Sanders and 3 more

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024
    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

13 authors.

F AbrarDepartment of Biology, University of Waterloo, Waterloo, Ontario, Canada.
M C DaviesMolecular and Cell Biology Cluster, School of Biosciences, University of Sheffield, Sheffield, UK.
Y AlshehabiDepartment of Biology, University of Waterloo, Waterloo, Ontario, Canada.
A KumarDepartment of Biology, University of Waterloo, Waterloo, Ontario, Canada.
A DangDepartment of Biology, University of Waterloo, Waterloo, Ontario, Canada.
Y T N NguyenDepartment of Medical Genetics, BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
J CollinsDepartment of Medical Genetics, BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
N S CaronDepartment of Medical Genetics, BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
J S ChoudharyCancer Biology Division, Functional Proteomics, Chester Beatty Laboratories, The Institute of Cancer Research, London, UK.
S S SandersDepartment of Medical Genetics, BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
M O CollinsMolecular and Cell Biology Cluster, School of Biosciences, University of Sheffield, Sheffield, UK.ORCID https://orcid.org/0000-0002-7656-4975
M R HaydenDepartment of Medical Genetics, BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
D D O MartinDepartment of Biology, University of Waterloo, Waterloo, Ontario, Canada.ORCID https://orcid.org/0000-0002-2407-1597

Funding

Canadian Government|Natural Sciences and Engineering Research Council of Canada (NSERC) RGPIN-2019-04617CIHR 154278CIHR FDNThe Royal Society RG150409
6 · The paper itself

Abstract

Disruption of autophagy has emerged as a common feature in many neurodegenerative diseases. Autophagy is a membrane-dependent pathway that requires many key regulators to quickly localize on and off membranes during induction, promoting membrane fusion. Previously, our bioinformatic approaches have shown that autophagy and Huntington disease (HD) are enriched in palmitoylated proteins. Palmitoylation involves the reversible addition of long-chain fatty acids to promote membrane binding. Herein, we show that inhibition of palmitoylation regulates the abundance of several key regulators of autophagy and leads to a partial block of autophagic flux. We confirm that the autophagy receptor SQSTM1/p62 (sequestosome 1) is palmitoylated and directed to the lysosome. Importantly, we report that SQSTM1 palmitoylation is significantly reduced in HD patient and mouse model brains. This finding reveals a novel mechanism contributing to the generation of empty autophagosomes previously seen in HD models and patient-derived cells.

Indexed as

AutophagyHuntington DiseaseLipoylationSequestosome-1 ProteinAnimalsAutophagosomesBrainHumansLysosomesMiceSequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID40326774
PMCPMC12054346

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.