ArticleThe Journal of cell biology2025
Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity.
Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Apical proximal tubule fatty acid uptake-generated ceramides cause endoplasmic reticulum stress from altered membrane fluidity.JCI insight · 2026Article
- Depression-induced systemic C16-ceramide deficiency promotes OSCC via attenuation of mitochondrial apoptosis.Cellular and molecular life sciences : CMLS · 2026Article
- Endolysosomal Impact of Elevated Ceramide Levels Revealed by Optical and Ultrastructural Nanoprobing.ACS nano · 2026Article
- Hesperidin alleviates systemic inflammation and oxidative stress by remodeling adipose tissue lipid metabolism in periparturient dairy cows.Journal of animal science and biotechnology · 2026Article
- Acid Ceramidase Inhibition Disrupts Ceramide Homeostasis and Induces Mitochondrial Apoptosis in IDH1-Mutant Oligodendroglioma.Research square · 2026Article
- Article
- Multi-omics-informed hydrogel design: modulating IL-6 to reduce endoplasmic reticulum stress in bone regeneration.Bioactive materials · 2026Article
- The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Exploring Ceramide C16:0 as a Novel Biomarker and Therapeutic Target for Atherosclerosis.Journal of the American Heart Association · 2026Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Under endoplasmic reticulum (ER) stress (ERS), cells initiate the unfolded protein response (UPR) to maintain ER homeostasis. Recent studies revealed ERS transmission between cells and tissues, by activating the cell-nonautonomous UPR in cells that do not experience ERS directly. Here, we report that ERS triggers a rapid release of ceramide independent of the UPR, but requiring the acid sphingomyelinase activity. Carried by lipoproteins, ceramide is delivered to receiving cells to induce the UPR and regulate cell functions at multiple aspects, including lipid accumulation, cell death, and cytokine production. Mechanistically, extracellular ceramide stimulates ceramide synthesis at the transcription level in receiving cells, leading to ceramide accumulation in the ER so as to reduce membrane fluidity to disrupt ER calcium homeostasis, thus activating the UPR. Sphingomyelin counterbalanced the effect of ceramide. UPR induction is the frontline response to protect cells from ceramide insult. Our study suggests ceramide-mediated ERS transmission as a universal cell-cell communication model regulating a wide range of physiological events.
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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.