ArticleNature communications2021
mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 418 papers, 1 of them a synthesis that pooled it.
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
418 citing papers in PubMed, 1 synthesis or guideline pooled it, 678 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Lapatinib suppresses cysteine deprivation-induced ferroptotic cell death by modulating mitochondrial function.Medical oncology (Northwood, London, England) · 2026Article
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.Functional & integrative genomics · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- SREBF2 promotes mitophagy and protects against ferroptosis via Cav-1-regulated PINK1/Parkin signaling in ischemic heart failure.Journal of molecular medicine (Berlin, Germany) · 2026Article
- MHY@MO@PPP inhibits ferroptosis positive feedback and delays the acute kidney injury-to-chronic kidney disease transition by remodeling the FeJournal of nanobiotechnology · 2026Article
- LKB1 Loss Sensitizes Lung Tumor Spheres to Mitomet-Induced Ferroptosis, and These Effects are Enhanced by mTOR Inhibition.Molecular carcinogenesis · 2026Article
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Valproic Acid Inhibits Ferroptosis and Improves Bone Integration in OVX Rats Through the AMPK/SIRT1 Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Gut-Liver Translocation of Bacteroides Uniformis Alleviates Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease by Suppressing Hepatocyte Ferroptosis via Propionic Acid Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond biochemical cascades: the biophysical execution of disulfidptosis via actin network collapse.Molecular biology reports · 2026Review
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- 5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells.Current issues in molecular biology · 2026Article
- A ferroptosis-suppressive state drives resistance to bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.Signal transduction and targeted therapy · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Cell-Type-Specific Regulation of Ferroptosis in Atherosclerosis: Mechanisms and Therapeutic Potential of Natural Products.Cell biochemistry and function · 2026Review
- USP43-mediated deubiquitination of SLC7A11 protects against LPS-induced acute lung injury by inhibiting ferroptosis.Clinical and translational medicine · 2026Article
- Huashi Baidu formula may attenuate adriamycin-induced myocardial injury via modulating NRF2-ATF3-SRXN1 axis-mediated ferroptosis.Chinese herbal medicines · 2026Article
358 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Glutathione peroxidase 4 (GPX4) utilizes glutathione (GSH) to detoxify lipid peroxidation and plays an essential role in inhibiting ferroptosis. As a selenoprotein, GPX4 protein synthesis is highly inefficient and energetically costly. How cells coordinate GPX4 synthesis with nutrient availability remains unclear. In this study, we perform integrated proteomic and functional analyses to reveal that SLC7A11-mediated cystine uptake promotes not only GSH synthesis, but also GPX4 protein synthesis. Mechanistically, we find that cyst(e)ine activates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) and promotes GPX4 protein synthesis at least partly through the Rag-mTORC1-4EBP signaling axis. We show that pharmacologic inhibition of mTORC1 decreases GPX4 protein levels, sensitizes cancer cells to ferroptosis, and synergizes with ferroptosis inducers to suppress patient-derived xenograft tumor growth in vivo. Together, our results reveal a regulatory mechanism to coordinate GPX4 protein synthesis with cyst(e)ine availability and suggest using combinatorial therapy of mTORC1 inhibitors and ferroptosis inducers in cancer treatment.
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.