ArticleNature communications2024
Methionine-SAM metabolism-dependent ubiquinone synthesis is crucial for ROS accumulation in ferroptosis induction.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Invoking ferroptosis and photon-controlled pyroptosisChemical science · 2026Article
- Pollen-expressed methionine synthases in Nicotiana tabacum regulate pollen development and germination.Plant physiology · 2026Article
- Dietary Methionine Affects Lipid Metabolism and Ferroptosis-Related Responses to Modulate Oxidative Stress Induced by High-Lipid-Diet in Golden Pompano (Antioxidants (Basel, Switzerland) · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Ferroptosis in Doxorubicin-Induced Cardiotoxicity: From Molecular Mechanisms to Therapeutic Strategies and Clinical Management Paradigms.Reviews in cardiovascular medicine · 2026Review
- L-Methionine attenuates methotrexate-induced cardiotoxicity by modulating oxidative stress, inflammation, and dyslipidemia in rats.Toxicology reports · 2026Article
- Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis.Cell reports · 2026Article
- Epigenetic Mechanisms Regulating Ferroptosis in Ischemic Stroke: From Pathogenesis to Therapeutic Targets.Cellular and molecular neurobiology · 2026Review
- Coenzyme Q10 exerts anti-cancer effects in bladder cancer by inducing ROS-mediated apoptosis and autophagy.Journal of bioenergetics and biomembranes · 2026Article
- Review
- Lithospermic Acid Improves Doxorubicin-Induced Cardiomyopathy Through Sirtuin-3-Mediated Deacetylation of p53.Phytotherapy research : PTR · 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
- Article
- Cysteine Restriction Induces Ferroptosis Depending on theGastro hep advances · 2026Article
- ACSL4-Mediated Ferroptosis and its Biological Functions and Potential Therapeutic Significance in Liver Diseases.Current pharmaceutical design · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Identification of disease ameliorated metabolite candidates from Gut Microbes and their interacting targets based on a novel estimating function.Frontiers in microbiology · 2026Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases.
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