ArticleMolecular cell2012
Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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
60 citing papers in PubMed, 114 citations in OpenAlex.
- ER proteostasis meets mitochondrial function: contact sites as hubs of communication and therapeutic targets.The FEBS journal · 2026Review
- Oxidative protein folding and CaCellular and molecular life sciences : CMLS · 2026Review
- Zinc-redox crosstalk regulates proteostasis in the endoplasmic reticulum.Nature communications · 2026Article
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- L-ascorbate prevents non-alcoholic steatohepatitis-based hepatocarcinogenesis in Sod1/Prdx4 double-knockout mice.Scientific reports · 2025Article
- Pyrazolone-based ERO1 inhibitors in ERO1-driven triple-negative breast cancer and SEPN1-related myopathy: Structure-activity relationship and therapeutic potential.Pharmacological research · 2025Article
- Selective inhibition of ERO1α with M6766, a novel small-molecule inhibitor, prevents arterial thrombosis and ischemic stroke in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Small molecule-mediated inhibition of the oxidoreductase ERO1A restrains aggressive breast cancer by impairing VEGF and PD-L1 in the tumor microenvironment.Cell death & disease · 2025Article
- ERO1A levels are a prognostic indicator in EGFR mutated non small cell lung cancer.NPJ precision oncology · 2024Article
- Endoplasmic Reticulum Oxidative Stress Promotes Glutathione-Dependent Oxidation of Collagen-1A1 and Promotes Lung Fibroblast Activation.American journal of respiratory cell and molecular biology · 2024Article
- Post-Translational Modifications to Cysteine Residues in Plant Proteins and Their Impact on the Regulation of Metabolism and Signal Transduction.International journal of molecular sciences · 2024Review
- SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA.Cell reports. Medicine · 2024Article
- Biological mechanisms and clinical significance of endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) in human cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Fingerprint of the oxido-reductase ERO1: A protein disulfide bond producer and supporter of cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway.Scientific reports · 2023Article
- Distinct role of ERp57 and ERdj5 as a disulfide isomerase and reductase during ER protein folding.Journal of cell science · 2023Article
- Endoplasmic reticulum oxidoreductin 1-alpha deficiency and activation of protein translation synergistically impair breast tumour resilience.British journal of pharmacology · 2022Article
- Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.Molecules (Basel, Switzerland) · 2022Review
- Ascorbate is a multifunctional micronutrient whose synthesis is lacking in primates.Journal of clinical biochemistry and nutrition · 2021Article
- The ER stress response mediator ERO1 triggers cancer metastasis by favoring the angiogenic switch in hypoxic conditions.Oncogene · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1α, ERO1β, and PRDX4 compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly modest delay in disulfide bond formation in secreted proteins but a profound, 5-fold lower procollagen 4-hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice, and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H(2)O(2)-generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation, and a noncanonical form of scurvy.
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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.