ArticleProceedings of the National Academy of Sciences of the United States of America2013
Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 395 papers.
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Who cites it
395 citing papers in PubMed, 652 citations in OpenAlex.
- Olivetol induces a non-genotoxic nucleolar DNA damage response via membrane-dependent stress signaling.Nucleus (Austin, Tex.) · 2026Article
- Mammalian MemPrep establishes the lipid composition of ER membranes in HEK293T cells.EMBO reports · 2026Article
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Loss of ceramide synthases 5 and 6 exacerbate myristate-induced colonic IRE1α activation.Journal of lipid research · 2026Article
- A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.Cancer cell · 2026Article
- Thbs1Journal of advanced research · 2026Article
- Apical proximal tubule fatty acid uptake-generated ceramides cause endoplasmic reticulum stress from altered membrane fluidity.JCI insight · 2026Article
- The membrane transition strongly enhances biopolymer condensation through prewetting.Nature chemical biology · 2026Article
- Review
- The complex lipidome as a driver of tissue-specific pathology in adrenoleukodystrophy.Molecular neurodegeneration · 2026Review
- The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation.Nature communications · 2026Article
- Beneficially Stressing the Peripheral Nervous System to Repair.International journal of molecular sciences · 2026Review
- Mechanosensing at the endoplasmic reticulum by IRE1.Research square · 2026Article
- Lipid droplets as stress-buffering organelles in cancer cell homeostasis.Communications biology · 2026Review
- A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics.Journal of experimental & clinical cancer research : CR · 2026Review
- Calcium-mediated calreticulin-IRE1α interaction drives dynamic fluctuation of IRE1α activity under chronic endoplasmic reticulum stress.Nature communications · 2026Article
- Lipid-dependent accrual of a subset of monocyte-derived macrophages is essential for tissue regeneration.Nature metabolism · 2026Article
- Dietary Ethanolamine Increases Hepatic Lipid Accumulation in Mice Fed a High-Fat Diet.The Journal of nutrition · 2026Article
- Remodeling of the cellular membrane architecture in response to BK polyomavirus infection.Virology journal · 2026Review
335 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress sensors use a related luminal domain to monitor the unfolded protein load and convey the signal to downstream effectors, signaling an unfolded protein response (UPR) that maintains compartment-specific protein folding homeostasis. Surprisingly, perturbation of cellular lipid composition also activates the UPR, with important consequences in obesity and diabetes. However, it is unclear if direct sensing of the lipid perturbation contributes to UPR activation. We found that mutant mammalian ER stress sensors, IRE1α and PERK, lacking their luminal unfolded protein stress-sensing domain, nonetheless retained responsiveness to increased lipid saturation. Lipid saturation-mediated activation in cells required an ER-spanning transmembrane domain and was positively regulated in vitro by acyl-chain saturation in reconstituted liposomes. These observations suggest that direct sensing of the lipid composition of the ER membrane contributes to the UPR.
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Registered trials
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.