Evidence map›Paper›PMID 39927758›Full record

ArticleeLife2025

Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids.

Xiuling Cao, Xiang Wu, Lei Zhao, Ju Zheng, Xuejiao Jin, Xinxin Hao, Joris Winderickx, Shenkui Liu, Lihua Chen, Beidong Liu

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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.

Xiuling Cao *State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.ORCID https://orcid.org/0000-0001-6940-4482
Xiang Wu *State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.
Lei Zhao *Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Ju ZhengDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Xuejiao JinState Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.
Xinxin HaoDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Joris WinderickxFunctional Biology, KU Leuven, Leuven, Belgium.ORCID https://orcid.org/0000-0003-3133-7733
Shenkui LiuState Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.
Lihua ChenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.ORCID https://orcid.org/0000-0003-3369-1875
Beidong LiuState Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.ORCID https://orcid.org/0000-0001-6052-8411

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2023A1515010483Cancerfonden 19 0069 and 23 2769 PjFellowship from China Scholarship Council and KU Leuven C14/17/063FWO-Vlaanderen G0C7222NKU Leuven C14/21/095National Natural Science Foundation of China 32000387Natural Science Foundation of Zhejiang Province LY23C060001Scientific Research Foundation of Zhejiang A and F University 2021LFR053Vetenskapsrådet VR 2019-03604 and 2023-03560
6 · The paper itself

Abstract

Due to proteostasis stress induced by aging or disease, misfolded proteins can form toxic intermediate species of aggregates and eventually mature into less toxic inclusion bodies (IBs). Here, using a yeast imaging-based screen, we identified 84 potential synphilin-1 (SY1) IB regulators and isolated the conserved sphingolipid metabolic components in the most enriched groups. Furthermore, we show that, in both yeast cells and mammalian cells, SY1 IBs are associated with mitochondria. Pharmacological inhibition of the sphingolipid metabolism pathway or knockout of its key genes results in a delayed IB maturation and increased SY1 cytotoxicity. We postulate that SY1 IB matures by association with the mitochondrion membrane, and that sphingolipids stimulate the maturation via their membrane-modulating function and thereby protecting cells from SY1 cytotoxicity. Our findings identify a conserved cellular component essential for IB maturation and suggest a mechanism by which cells may detoxify the pathogenic protein aggregates through forming mitochondrion-associated IBs.

Indexed as

Carrier ProteinsInclusion BodiesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSphingolipidsAnimalsHumansMitochondriaCarrier ProteinsSaccharomyces cerevisiae ProteinsSphingolipidsgeneticsgenomicsimaging-based screeninclusion bodiesmammalian cellsmitochondrionS. cerevisiaesphingolipidssynphilin-1

Identifiers

PMID39927758
PMCPMC11810108

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.