ArticleRedox biology2024
Cysteine and homocysteine can be exploited by GPX4 in ferroptosis inhibition independent of GSH synthesis.
Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 78 citations in OpenAlex.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Engineered Substrates for a Sulfurtransferase Enhance Endogenous Hydropersulfides and Inhibit Ferroptosis.Angewandte Chemie (International ed. in English) · 2026Article
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- Review
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- Baicalein Attenuates High Glucose and Sodium Palmitate-Induced Ferroptosis in Cardiomyocytes via the Nrf2/SLC7A11/GPX4 Signaling Pathway.International journal of molecular sciences · 2026Article
- Synergistic Effects of Selenium, Selenoproteins, Selenocysteine and Procyanidin A2 Based on Immune Response and Oxidative Stress.Molecules (Basel, Switzerland) · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Dual-responsive polypyridyl Ru(II)-scaffolded hydrogel for trinitarian tumor therapy activated by mono-wavelength photo-irradiation.Journal of nanobiotechnology · 2026Article
- A Single Polyoxometalate Nanozyme for Cross-Reactive Thiol Array Sensing via pKa-Driven and Enrichment-Synergistic Strategy.Sensors (Basel, Switzerland) · 2026Article
- Cutibacterium acnes-Derived Extracellular Vesicles Promote Epithelial Ovarian Cancer Progression by Activating the KEAP1-NRF2 Antioxidant Pathway to Suppress Ferroptosis.Microbial biotechnology · 2026Article
- Relationship between different modes of death and premature ovarian insufficiency: a literature review.Apoptosis : an international journal on programmed cell death · 2026Review
- Dual tumor microenvironment-responsive albumin nanoplatform integrates conditional PROTAC activation with starvation and ferroptosis for synergistic cancer therapy.Journal of nanobiotechnology · 2026Article
- AQP7 Protects Vitrified Sheep GV-Stage Oocyte Maturation via Mitochondrial Activity.Animals : an open access journal from MDPI · 2026Article
- Selenomethionine as a dual-mechanism ferroptosis inhibitor: selenium-supply-driven GPX4 biosynthesis beyond transsulfuration and reductive-capacity-mediated ROS scavenging independent of GPX4 activity.Cell death & disease · 2026Article
- HSP70 Interactome-Mediated Proteolysis Targeting Chimera (HSP70-PROTAC) for Ferroptosis-Driven Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research progress on the regulation of ferroptosis in NPC (Review).Oncology reports · 2026Review
- Extracellular Metabolites and Natural Killer Cell Antitumor Function: Mechanisms and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Reactive oxygen species (ROS) in cancer: from redox signaling and metabolic plasticity to therapeutic vulnerabilities.Exploration of targeted anti-tumor therapy · 2026Review
- Magnolol triggers ferroptosis in triple-negative breast cancer through modulation of the ETS2/SLC7A11/GPX4 signaling axis.Frontiers in pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is inhibited by glutathione peroxidase 4 (GPX4), an antioxidant enzyme that uses reduced glutathione (GSH) as a cofactor to detoxify lipid hydroperoxides. As a selenoprotein, the core function of GPX4 is the thiol-dependent redox reaction. In addition to GSH, other small molecules such as cysteine and homocysteine also contain thiols; yet, whether GPX4 can exploit cysteine and homocysteine to directly detoxify lipid hydroperoxides and inhibit ferroptosis has not been addressed. In this study, we found that cysteine and homocysteine inhibit ferroptosis in a GPX4-dependent manner. However, cysteine inhibits ferroptosis independent of GSH synthesis, and homocysteine inhibits ferroptosis through non-cysteine and non-GSH pathway. Furthermore, we used molecular docking and GPX4 activity analysis to study the binding patterns and affinity between GPX4 and GSH, cysteine, and homocysteine. We found that besides GSH, cysteine and homocysteine are also able to serve as substrates for GPX4 though the affinities of GPX4 with cysteine and homocysteine are lower than that with GSH. Importantly, GPX family and the GSH synthetase pathway might be asynchronously evolved. When GSH synthetase is absent, for example in Flexibacter, the fGPX exhibits higher affinity with cysteine and homocysteine than GSH. Taken together, the present study provided the understanding of the role of thiol-dependent redox systems in protecting cells from ferroptosis and propose that GSH might be a substitute for cysteine or homocysteine to be used as a cofactor for GPX4 during the evolution of aerobic metabolism.
Indexed as
Identifiers
What OpenQuestion holds
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.