ArticleMolecular biology of the cell2017
Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Sphingolipid metabolic enzyme GLA expression in gliomas: prognostic implications and therapeutic potential.Frontiers in oncology · 2026Article
- Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.PLoS genetics · 2025Article
- Dysregulation of ceramide metabolism causes phytoceramide-dependent induction of the unfolded protein response.Molecular biology of the cell · 2024Article
- Loss of transcriptional regulator of phospholipid biosynthesis alters post-translational modification of Sec61 translocon beta subunit Sbh1 inmicroPublication biology · 2024Article
- The ERAD system is restricted by elevated ceramides.Science advances · 2023Article
- An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.Science advances · 2023Article
- Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches.Frontiers in cell and developmental biology · 2022Review
- Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation.PloS one · 2021Article
- The characteristics of host lipid body biogenesis during coral-dinoflagellate endosymbiosis.PeerJ · 2021Article
- The yeastJournal of cell science · 2020Article
- Protein Quality Control and Lipid Droplet Metabolism.Annual review of cell and developmental biology · 2020Review
- Loss of ERAD bridging factor UBX2 modulates lipid metabolism and leads to ER stress-associated apoptosis during cadmium toxicity in Saccharomyces cerevisiae.Current genetics · 2020Article
- Disorders of FZ-CRD; insights towards FZ-CRD folding and therapeutic landscape.Molecular medicine (Cambridge, Mass.) · 2019Review
- Dynamics and functions of lipid droplets.Nature reviews. Molecular cell biology · 2019Review
- The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis.Journal of cell science · 2019Article
- Dropping in on lipid droplets: insights into cellular stress and cancer.Bioscience reports · 2018Review
- Lipid Synthesis Is Required to Resolve Endoplasmic Reticulum Stress and Limit Fibrotic Responses in the Lung.American journal of respiratory cell and molecular biology · 2018Article
- A VCP inhibitor substrate trapping approach (VISTA) enables proteomic profiling of endogenous ERAD substrates.Molecular biology of the cell · 2018Article
- A Proximity Labeling Strategy Provides Insights into the Composition and Dynamics of Lipid Droplet Proteomes.Developmental cell · 2018Article
- Establishing the lipid droplet proteome: Mechanisms of lipid droplet protein targeting and degradation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD. However, whether LDs are involved in the ERAD process remains an outstanding question. Using chemical and genetic approaches to disrupt diacylglycerol acyltransferase (DGAT)-dependent LD biogenesis, we provide evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our results suggest that triacsin C causes global alterations in the cellular lipid landscape that disrupt ER proteostasis by interfering with the glycan trimming and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the IRE1 and PERK branches of the unfolded protein response and ultimately leads to IRE1-dependent cell death. These findings identify an intimate relationship between fatty acid metabolism and ER proteostasis that influences cell viability.
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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.