ArticleThe EMBO journal2023
Thiol reductive stress activates the hypoxia response pathway.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Loss of Echs1 in neural stem and progenitor cells impairs neurogenesis via ER stress activation and lipid metabolic reprogramming.Nature communications · 2026Article
- RNA methyltransferase CMTR-1 inhibition activates a GATA transcription factor-mediated protective immune response.PLoS pathogens · 2026Article
- Evaluation of Alkaline-Labile Sulfane Sulfur in Biological Samples: The Influence of Hyperhomocysteinemia and Oxidative Stress.Biomolecules · 2026Article
- Over-Intake of Plant-Derived Antioxidants, HInternational journal of molecular sciences · 2026Article
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- Extracellular Vesicles, Nutrient Balance, and Redox Metabolism During Epididymal Sperm Maturation: A Perspective on the Complexity of Intercellular Interplay.Advances in anatomy, embryology, and cell biology · 2026Review
- RNA methyltransferase CMTR-1 inhibition activates a GATA transcription factor-mediated protective immune response.bioRxiv : the preprint server for biology · 2025Article
- Dithiothreitol induced endoplasmic reticulum stress and its role in neurodegeneration inWorld journal of biological chemistry · 2025Article
- Iron-deplete diet enhances Caenorhabditis elegans lifespan via oxidative stress response pathways.The EMBO journal · 2025Article
- Fine-Tuning of the Endoplasmic Reticulum Stress Response Mechanism Plays a Key Role in Cellular Survival-A Mathematical Study.International journal of molecular sciences · 2025Article
- Bacterial metabolism of tryptophan causes toxicity inbioRxiv : the preprint server for biology · 2025Article
- An acyltransferase protectsbioRxiv : the preprint server for biology · 2025Article
- Iron-deplete diet enhancesbioRxiv : the preprint server for biology · 2025Article
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- Conserved lipid metabolic reprogramming confers hypoxic and aging resilience.bioRxiv : the preprint server for biology · 2025Article
- A new peptide inhibitor of C1QBP exhibits potent anti-tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair.Clinical and translational medicine · 2025Article
- Innate immune and endoplasmic reticulum unfolded protein response pathways protectJournal of biosciences · 2025Article
- Article
- Calcineurin inhibition enhanceseLife · 2024Article
- Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Owing to their capability to disrupt the oxidative protein folding environment in the endoplasmic reticulum (ER), thiol antioxidants, such as dithiothreitol (DTT), are used as ER-specific stressors. We recently showed that thiol antioxidants modulate the methionine-homocysteine cycle by upregulating an S-adenosylmethionine-dependent methyltransferase, rips-1, in Caenorhabditis elegans. However, the changes in cellular physiology induced by thiol stress that modulate the methionine-homocysteine cycle remain uncharacterized. Here, using forward genetic screens in C. elegans, we discover that thiol stress enhances rips-1 expression via the hypoxia response pathway. We demonstrate that thiol stress activates the hypoxia response pathway. The activation of the hypoxia response pathway by thiol stress is conserved in human cells. The hypoxia response pathway enhances thiol toxicity via rips-1 expression and confers protection against thiol toxicity via rips-1-independent mechanisms. Finally, we show that DTT might activate the hypoxia response pathway by producing hydrogen sulfide. Our studies reveal an intriguing interaction between thiol-mediated reductive stress and the hypoxia response pathway and challenge the current model that thiol antioxidant DTT disrupts only the ER milieu in the cell.
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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.