ArticleProceedings of the National Academy of Sciences of the United States of America2014
Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 180 citations in OpenAlex.
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- Distinct S-adenosylmethionine synthases link phosphatidylcholine to mitochondrial function and stress survival.PLoS biology · 2025Article
- Vitamin BResearch square · 2025Article
- Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging.Nature neuroscience · 2025Article
- Reprograming gene expression in 'hibernating'eLife · 2025Article
- Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.PLoS genetics · 2025Article
- Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated worms.PloS one · 2025Article
- Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response.Cold Spring Harbor perspectives in biology · 2024Review
- MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.Cell death discovery · 2024Article
- The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks.G3 (Bethesda, Md.) · 2024Article
- MemPrep, a new technology for isolating organellar membranes provides fingerprints of lipid bilayer stress.The EMBO journal · 2024Article
- Heat Shock Proteins Function as Signaling Molecules to Mediate Neuron-Glia Communication During Aging.bioRxiv : the preprint server for biology · 2024Article
- Article
- A viable hypomorphic mutation in the mitochondrial ribosome subunit, MRPS-31, exhibits mitochondrial dysfunction inmicroPublication biology · 2024Article
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.Biomedicines · 2023Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
The Mediator is a conserved transcriptional coregulator complex required for eukaryotic gene expression. In Caenorhabditis elegans, the Mediator subunit mdt-15 is essential for the expression of genes involved in fatty acid metabolism and ingestion-associated stress responses. mdt-15 loss of function causes defects in reproduction and mobility and shortens lifespan. In the present study, we find that worms with mutated or depleted mdt-15 (mdt-15 worms) exhibit decreased membrane phospholipid desaturation, especially in phosphatidylcholine. Accordingly, mdt-15 worms exhibit disturbed endoplasmic reticulum (ER) homeostasis, as indicated by a constitutively activated ER unfolded protein response (UPR(ER)). Activation of this stress response is only partially the consequence of reduced membrane lipid desaturation, implicating other mdt-15-regulated processes in maintaining ER homeostasis. Interestingly, mdt-15 inactivation or depletion of the lipid metabolism enzymes stearoyl-CoA-desaturases (SCD) and S-adenosyl methionine synthetase (sams-1) activates the UPR(ER) without promoting misfolded protein aggregates. Moreover, these worms exhibit wild-type sensitivity to chemically induced protein misfolding, and they do not display synthetic lethality with mutations in UPR(ER) genes, which cause protein misfolding. Therefore, the constitutively activated UPR(ER) in mdt-15, SCD, and sams-1 worms is not the consequence of proteotoxic stress but likely is the direct result of changes in ER membrane fluidity and composition. Together, our data suggest that the UPR(ER) is induced directly upon membrane disequilibrium and thus monitors altered ER homeostasis.
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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.