ArticleCell metabolism2021
Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis.
Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 2 of them syntheses that pooled it.
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Who cites it
218 citing papers in PubMed, 2 syntheses or guidelines pooled it, 325 citations in OpenAlex.
- Mechanism and role of ferroptosis in the development of gastric cancer.Clinical and experimental medicine · 2025Pooled it
- Research progress on ferroptosis in diabetic kidney disease.Frontiers in endocrinology · 2022Pooled it
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Lung cancer metabolism: a dynamic and adaptive network.Cellular and molecular life sciences : CMLS · 2026Review
- An excitation-customized ICT-type turn-on probe for visualization of cysteine fluctuation in diverse drug-induced ferroptosis pathways.Analytical and bioanalytical chemistry · 2026Article
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Article
- IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.Nature communications · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- A targetable ALDH3A2-NRF2 axis mediates KEAP1-mutant tumour development via ferroptosis inhibition.Cell death and differentiation · 2026Article
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- A targetable FTO/SLC7A11/CBS/CTH axis controls cysteine metabolism, growth and survival in NSCLC.Science advances · 2026Article
- White matter injury in neonatal rats is attenuated by GsMTx4 inhibiting oligodendrocyte precursor cell ferroptosis via the PIEZO1/GCLC signaling pathway.Pediatric research · 2026Article
- Curcumin Protects Mouse Spermatogonia from Triptolide-Induced Injury Through Modulation of Ferroptosis-Related Pathways.Biology · 2026Article
- Mechanism of palytoxin-induced ferroptosis in HaCaT cells via targeting TrxR1.Cell biology and toxicology · 2026Article
- Review
- SERPINE2-mediated activation of JAK2/STAT3 facilitates NRF2 nuclear translocation and GCLC transcription to confer ferroptosis resistance and lenvatinib resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting taurine metabolism via PROTAC-mediated SLC6A6 degradation potentiates photodynamic therapy and reverses immunosuppression in cholangiocarcinoma.Journal of nanobiotechnology · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Rhein Prevents APAP-induced drug-induced Liver Injury by Upregulating Nrf2 and Inhibiting APAP-activating Enzymes.Cell biochemistry and biophysics · 2026Article
158 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cysteine is required for maintaining cellular redox homeostasis in both normal and transformed cells. Deprivation of cysteine induces the iron-dependent form of cell death known as ferroptosis; however, the metabolic consequences of cysteine starvation beyond impairment of glutathione synthesis are poorly characterized. Here, we find that cystine starvation of non-small-cell lung cancer cell lines induces an unexpected accumulation of γ-glutamyl-peptides, which are produced due to a non-canonical activity of glutamate-cysteine ligase catalytic subunit (GCLC). This activity is enriched in cell lines with high levels of NRF2, a key transcriptional regulator of GCLC, but is also inducible in healthy murine tissues following cysteine limitation. γ-glutamyl-peptide synthesis limits the accumulation of glutamate, thereby protecting against ferroptosis. These results indicate that GCLC has a glutathione-independent, non-canonical role in the protection against ferroptosis by maintaining glutamate homeostasis under cystine starvation.
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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.