ArticleScientific reports2016
Crosstalk between cystine and glutathione is critical for the regulation of amino acid signaling pathways and ferroptosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 168 citations in OpenAlex.
- Trial
- Repurposing approved drugs as ferroptosis modulators: a critical review of clinical trials in cancer and neurodegeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Pim1 Mitigates Heart Failure by Suppressing Ferroptosis Via Activation of the mTORC1/SLC7A11/GPX4 Axis.Journal of cardiovascular translational research · 2026Article
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Deuterated Polyunsaturated Fatty Acids AlleviatebioRxiv : the preprint server for biology · 2025Article
- Article
- Comparative transcriptome analysis reveals the complex response mechanisms of soybean leaves and roots to salt stress.BMC plant biology · 2025Article
- Context-dependent serotonin signaling links dietary quality to foraging decisions.Nature communications · 2025Article
- l-Cysteine-Glutathione Mixed Disulfide, a Novel Bioavailable Sulfhydryl-Modified Glutathione Precursor, Protects against Early Liver Injury Induced by Short-Term Hypercholesterolemia.Chemical research in toxicology · 2025Article
- Phosphatidylserine exposure and plasma membrane perforation as ferroptotic signatures for in vivo imaging.Npj imaging · 2025Article
- Study on the Mechanism of FOXA2 Activation on Glutathione Metabolic Reprogramming Mediated by ETV4 Transcription to Facilitate Colorectal Cancer Malignant Progression.Biochemical genetics · 2025Article
- MicroRNAs at the crossroads of exercise and ferroptosis: a regulatory bridge.Clinical and experimental medicine · 2025Review
- Host glutathione is required for Rickettsia parkeri cell division and intracellular survival.Nature communications · 2025Article
- Tryptophan Metabolic Enzyme IL4I1 Inhibits Ferroptosis by Decreasing Ubiquitination of Nrf2 via I3P in Glioblastoma.Cell proliferation · 2025Article
- Nanotherapeutics induced redox resetting of oxidative and nitrosative stress: targeting glutathione-depletion in cancer.Nanomedicine (London, England) · 2025Review
- Heat stress mitigation during prepartum and postpartum altered the plasma metabolome in Bos indicus-influenced cow-calf pairs.Journal of animal science · 2025Article
- Alterations in Glutathione Redox Homeostasis in Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review.Antioxidants (Basel, Switzerland) · 2024Review
- Ferroptosis in ischemic stroke: Animal models and mechanisms.Zoological research · 2024Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although essential amino acids regulate mechanistic target of rapamycin complex 1 (mTORC1) and the integrated stress response (ISR), the role of cysteine is unknown. We found that in hepatoma HepG2 cells, cystine (oxidized form of cysteine) activated mTORC1 and suppressed the ISR. Cystine deprivation induced GSH efflux and extracellular degradation, which aimed to restore cellular cysteine. Inhibition of γ-glutamyl transpeptidase (GGT) impaired the ability of GSH or cell-permeable GSH to restore mTORC1 signaling and the ISR, suggesting that the capacity of GSH to release cysteine, but not GSH per se, regulated the signaling networks. Inhibition of protein translation restored both mTORC1 signaling and the ISR during cystine starvation, suggesting the bulk of cellular cysteine was committed to the biosynthetic process. Cellular cysteine and GSH displayed overlapping protective roles in the suppression of ferroptosis, further supporting their cooperation in the regulation of cell signaling. Thus, cellular cysteine and its derivative GSH cooperate to regulate mTORC1 pathway, the ISR and ferroptosis.
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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.