ArticleNature communications2015
Dietary methionine can sustain cytosolic redox homeostasis in the mouse liver.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 107 citations in OpenAlex.
- Mitochondrial redox homeostasis links organellar stress surveillance to germline and somatic integrity in Caenorhabditis elegans.Redox biology · 2026Article
- Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency.Nature chemical biology · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.Redox biology · 2025Article
- Pleiotropic anti-cancer activities of novel non-covalent thioredoxin reductase inhibitors against triple negative breast cancer.Free radical biology & medicine · 2025Article
- Methionine-SAM metabolism-dependent ubiquinone synthesis is crucial for ROS accumulation in ferroptosis induction.Nature communications · 2024Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.Nature communications · 2024Article
- TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.The EMBO journal · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner.Redox biology · 2024Article
- Unresolved questions regarding cellular cysteine sources and their possible relationships to ferroptosis.Advances in cancer research · 2024Review
- A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses.Nature communications · 2023Article
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- Transsulfuration, minor player or crucial for cysteine homeostasis in cancer.Trends in cell biology · 2022Review
- Ferroptosis and its role in skeletal muscle diseases.Frontiers in molecular biosciences · 2022Review
- Silibinin Schiff Base Derivatives Counteract CClDrug design, development and therapy · 2022Article
- Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than auranofin.Redox biology · 2021Article
- The SARS-CoV-2 induced targeted amino acid profiling in patients at hospitalized and convalescent stage.Bioscience reports · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Across phyla, reduced nicotinamide adenine dinucleotide phosphate (NADPH) transfers intracellular reducing power to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR), thereby supporting fundamental housekeeping and antioxidant pathways. Here we show that a third, NADPH-independent pathway can bypass the need for TrxR1 and GR in mammalian liver. Most mice genetically engineered to lack both TrxR1 and GR in all hepatocytes ('TR/GR-null livers') remain long-term viable. TR/GR-null livers cannot reduce oxidized glutathione disulfide using NADPH but still require continuous glutathione synthesis. Inhibition of cystathionine γ-lyase causes rapid necrosis of TR/GR-null livers, indicating that methionine-fueled trans-sulfuration supplies the necessary cysteine precursor for glutathione synthesis via an NADPH-independent pathway. We further show that dietary methionine provides the cytosolic disulfide-reducing power and all sulfur amino acids in TR/GR-null livers. Although NADPH is generally considered an essential reducing currency, these results indicate that hepatocytes can adequately sustain cytosolic redox homeostasis pathways using either NADPH or methionine.
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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.