ReviewAntioxidants & redox signaling2013
The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities.
Review in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 588 papers, 1 of them a synthesis that pooled it.
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Who cites it
588 citing papers in PubMed, 1 synthesis or guideline pooled it, 933 citations in OpenAlex.
- xCT (Slc7a11) Regulation: Lessons from Cancer Research.Neurochemical research · 2026Pooled it
- Dual-mechanism vitamin C delivery by polyethylene glycol-23 glyceryl distearate-based niosomes via SVCT2 induction and enhanced transdermal penetration.Drug delivery · 2026Article
- Sustained Ion Imbalances Enhance Ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Upregulation of circSUCO22-20 in schizophrenia: clinical correlation with systemic inflammation and in vitro pro-apoptotic mechanisms.European archives of psychiatry and clinical neuroscience · 2026Article
- Imaging xCT with Immuno-PET in Therapy-Resistant Non-Small Cell Lung Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- SLC7A11-mediated disulfidptosis underlies the pathogenesis of proliferative diabetic retinopathy.Eye and vision (London, England) · 2026Article
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- Phase 1 dose-escalation trial combining sulfasalazine and stereotactic radiosurgery in patients with recurrent glioblastoma.Redox biology · 2026Article
- Emerging Role of Ferroptosis in Chemotherapy-Associated Hepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives.ACS pharmacology & translational science · 2026Review
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Ferroptosis Resistance: Redundant Antioxidant Networks Are a Barrier to Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Ratiometric iGluSnFr imaging to assess tonic glutamate in the cerebral cortex.bioRxiv : the preprint server for biology · 2026Article
- Phase I trial combining sulfasalazine and gamma knife radiosurgery for recurrent glioblastoma.MethodsX · 2026Article
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Placental ferroptosis and impaired fetal growth in symptomatic and asymptomatic SARS-CoV-2 infections.Clinical science (London, England : 1979) · 2026Article
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Non-coding RNAs as master regulators of ferroptosis in cancer: mechanisms and clinical implications.Molecular cancer · 2026Review
528 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
The antiporter system x(c)(-) imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system x(c)(-) is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system x(c)(-), including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system x(c)(-). Moreover, the roles of system x(c)(-) in regulating GSH levels, the redox state of the extracellular cystine/cysteine redox couple, and extracellular glutamate levels are discussed. In vitro, glutamate-mediated system x(c)(-) inhibition leads to neuronal cell death, a paradigm called oxidative glutamate toxicity, which has successfully been used to identify neuroprotective compounds. In vivo, xCT has a rather restricted expression pattern with the highest levels in the CNS and parts of the immune system. System x(c)(-) is also present in the eye. Moreover, an elevated expression of xCT has been reported in cancer. We highlight the diverse roles of system x(c)(-) in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS.
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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.