ArticleJournal of cell science2020
The mammalian cytosolic thioredoxin reductase pathway acts via a membrane protein to reduce ER-localised proteins.
Article in Journal of cell science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.Nature cell biology · 2026Article
- SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation.Nature genetics · 2026Article
- Cell Surface Thiol Engineering Mechanoregulates Myogenic Differentiation via the FAK-PI3K-AKT Axis.Advanced healthcare materials · 2026Article
- SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis.Molecular cell · 2025Article
- Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer.Nature genetics · 2025Article
- Review
- Development of luciferase-based highly sensitive reporters that detect ER-associated protein biogenesis abnormalities.iScience · 2024Article
- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- Subcellular Localization of Thioredoxin/Thioredoxin Reductase System-A Missing Link in Endoplasmic Reticulum Redox Balance.International journal of molecular sciences · 2024Article
- Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma.Nature cancer · 2024Article
- Distinct role of ERp57 and ERdj5 as a disulfide isomerase and reductase during ER protein folding.Journal of cell science · 2023Article
- Introduction of a More Glutaredoxin-like Active Site to PDI Results in Competition between Protein Substrate and Glutathione Binding.Antioxidants (Basel, Switzerland) · 2022Article
- THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer.EMBO molecular medicine · 2022Article
- Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.Biomolecules · 2022Review
- ER Redox Homeostasis Regulates Proinsulin Trafficking and Insulin Granule Formation in the Pancreatic Islet β-Cell.Function (Oxford, England) · 2022Article
- Pathways Linking Nicotinamide Adenine Dinucleotide Phosphate Production to Endoplasmic Reticulum Protein Oxidation and Stress.Frontiers in molecular biosciences · 2022Review
- A cytosolic reductase pathway is required for efficient N-glycosylation of an STT3B-dependent acceptor site.Journal of cell science · 2021Article
- Mechanisms of Disulfide Bond Formation in Nascent Polypeptides Entering the Secretory Pathway.Cells · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Folding of proteins entering the mammalian secretory pathway requires the insertion of the correct disulfides. Disulfide formation involves both an oxidative pathway for their insertion and a reductive pathway to remove incorrectly formed disulfides. Reduction of these disulfides is crucial for correct folding and degradation of misfolded proteins. Previously, we showed that the reductive pathway is driven by NADPH generated in the cytosol. Here, by reconstituting the pathway using purified proteins and ER microsomal membranes, we demonstrate that the thioredoxin reductase system provides the minimal cytosolic components required for reducing proteins within the ER lumen. In particular, saturation of the pathway and its protease sensitivity demonstrates the requirement for a membrane protein to shuttle electrons from the cytosol to the ER. These results provide compelling evidence for the crucial role of the cytosol in regulating ER redox homeostasis, ensuring correct protein folding and facilitating the degradation of misfolded ER proteins.
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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.