ArticleScience advances2023
The ERAD system is restricted by elevated ceramides.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis.Journal of advanced research · 2026Article
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Decoding the impact of lipid saturation on ER signaling networks, ERSU, UPR, and ERAD.PloS one · 2026Article
- Competition between Der1 and ERAD-M substrates controls Hrd1 complex function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- Ubiquitin chain variability directs substrates of the Tul1 ubiquitin ligase complex to different degradation pathways.The Journal of cell biology · 2025Article
- Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.PLoS genetics · 2025Article
- A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8Nature metabolism · 2025Article
- Disrupting cholesterol homeostasis in T cells boosts antitumour responses.Nature metabolism · 2025Article
- Role of lipids in interorganelle communication.Trends in cell biology · 2025Review
- Article
- Dysregulation of ceramide metabolism causes phytoceramide-dependent induction of the unfolded protein response.Molecular biology of the cell · 2024Article
- Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen.bioRxiv : the preprint server for biology · 2024Article
- Loss of transcriptional regulator of phospholipid biosynthesis alters post-translational modification of Sec61 translocon beta subunit Sbh1 inmicroPublication biology · 2024Article
- Deep mutational scanning highlights a role for cytosolic regions in Hrd1 function.Cell reports · 2023Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- Membrane homeostasis beyond fluidity: control of membrane compressibility.Trends in biochemical sciences · 2023Review
- Featured interactome of homocysteine-inducible endoplasmic reticulum protein uncovers novel binding partners in response to ER stress.Computational and structural biotechnology journal · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Misfolded proteins in the endoplasmic reticulum (ER) are removed through a process known as ER-associated degradation (ERAD). ERAD occurs through an integral membrane protein quality control system that recognizes substrates, retrotranslocates the substrates across the membrane, and ubiquitinates and extracts the substrates from the membrane for degradation at the cytosolic proteasome. While ERAD systems are known to regulate lipid biosynthetic enzymes, the regulation of ERAD systems by the lipid composition of cellular membranes remains unexplored. Here, we report that the ER membrane composition influences ERAD function by incapacitating substrate extraction. Unbiased lipidomic profiling revealed that elevation of specific very-long-chain ceramides leads to a marked increase in the level of ubiquitinated substrates in the ER membrane and concomitantly reduces extracted substrates in the cytoplasm. This work reveals a previously unrecognized mechanism in which ER membrane lipid remodeling changes the activity of ERAD.
Identifiers
What OpenQuestion holds
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.