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Record W4410794720 · doi:10.1073/pnas.2422126122

Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast

2025· article· en· W4410794720 on OpenAlexfundno aff
Yojiro Hoshikawa, Natsuho Shirota, Hiroshi Tsugawa, Satoshi Kimura, Akihisa Matsuyama, Yoko Yashiroda, Hideaki Kakeya, Makoto Arita, Reiko Iizumi, Minoru Yoshida, Shinichi Nishimura

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPhotosynthetic Processes and Mechanisms
Canadian institutionsnot available
FundersMoonshot Research and Development ProgramExploratory Research for Advanced TechnologyKeio UniversityJapan Science and Technology AgencyTokyo University of Agriculture and TechnologyUniversity of California, San DiegoTokyo University of AgricultureUniversity of TorontoJapan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and TechnologyNational Bioscience Database CenterJapan Agency for Medical Research and DevelopmentRIKENUniversity of Tokyo
KeywordsLipotoxicityGlycerophospholipidsEndoplasmic reticulumSchizosaccharomycesPentadecanoic acidBiologyPalmitoleic acidSchizosaccharomyces pombeBiochemistryFatty acidYeastCell biologyChemistrySaccharomyces cerevisiaeLinoleic acidEndocrinology

Abstract

fetched live from OpenAlex

Excess amounts of saturated fatty acids (FAs) are toxic to organisms, a condition termed lipotoxicity, which is often accompanied by pleiotropic cellular and tissue dysfunction. Here, we show that pentadecanoic acid (C15:0) exerts toxicity on the fission yeast Schizosaccharomyces pombe by generating an aberrantly planar endoplasmic reticulum (ER) structure, which we named a “giant ER sheet.” Untargeted lipidomics revealed that C15:0 is incorporated into complex lipids depending on an acyl-CoA ligase Lcf1 and an acyl-CoA transferase Slc1, thereby increasing the saturation level of the acyl chains. The toxicity and giant ER sheet formation were abolished by deleting lcf1 or slc1 gene, indicating that the incorporation of C15:0 into glycerophospholipids causes giant ER sheet formation. The giant ER sheets disrupted the correct migration of Mid1, a protein determining the cell division site, and physically blocked septum formation, hindering correct cell separation. Our results suggest that the ER is the primary site targeted by saturated FAs, leading to lipotoxicity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.287
Teacher spread0.270 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

Explore more

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