ArticleNature cell biology2022
PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 328 papers.
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Who cites it
328 citing papers in PubMed, 519 citations in OpenAlex.
- FXYD5 promotes the growth of glioblastoma by targeting the PI3K/AKT/ACSL4 signaling axis.Oncology reports · 2026Article
- Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis.Journal of physiology and biochemistry · 2026Article
- Exosomal circPDSS1 Derived From Gastric Cancer Cells Promotes Natural Killer Cell Ferroptosis by Regulating the miR-142-3p/ACSL4 Molecular Axis.Applied biochemistry and biotechnology · 2026Article
- Radiotherapy-Induced Side Effects: Epidemiology, Pathogenesis, Prevention and Treatments.MedComm · 2026Review
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Sustained Ion Imbalances Enhance Ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Article
- Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026Review
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- Whole-body mass spectrometry imaging reveals metabolome and lipid peroxidation heterogeneity in zebrafish xenografts of esophageal squamous cell carcinoma.Analytical and bioanalytical chemistry · 2026Article
- Targeting the PHB2-ACSL3 Lipid-Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RanBP2 promotes ferroptosis resistance and compromises therapeutic response by stabilizing SLC7A1 through LRSAM1 SUMOylation and ubiquitination in lung adenocarcinoma.Cell death and differentiation · 2026Article
- Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.Nature cancer · 2026Article
- SUV39H2-mediated NCOA4 methylation controls ferritinophagy and ferroptosis in triple-negative breast cancer.Cell death & disease · 2026Article
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Ferroptosis in retinal pigment epithelial cells: Current status and future developments.Indian journal of ophthalmology · 2026Review
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Ferroptosis in prostatitis: pathogenic mechanisms and therapeutic advances.Molecular and cellular biochemistry · 2026Review
- HIF-1α enhances ferroptosis resistance in anaplastic thyroid carcinoma by suppressing ACSL4-mediated lipid metabolic homeostasis.Cellular & molecular biology letters · 2026Article
- Molecular mechanisms of FSP1-regulated ferroptosis and therapeutic implications in various cancers.Cellular & molecular biology letters · 2026Review
268 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The accumulation of lipid peroxides is recognized as a determinant of the occurrence of ferroptosis. However, the sensors and amplifying process of lipid peroxidation linked to ferroptosis remain obscure. Here we identify PKCβII as a critical contributor of ferroptosis through independent genome-wide CRISPR-Cas9 and kinase inhibitor library screening. Our results show that PKCβII senses the initial lipid peroxides and amplifies lipid peroxidation linked to ferroptosis through phosphorylation and activation of ACSL4. Lipidomics analysis shows that activated ACSL4 catalyses polyunsaturated fatty acid-containing lipid biosynthesis and promotes the accumulation of lipid peroxidation products, leading to ferroptosis. Attenuation of the PKCβII-ACSL4 pathway effectively blocks ferroptosis in vitro and impairs ferroptosis-associated cancer immunotherapy in vivo. Our results identify PKCβII as a sensor of lipid peroxidation, and the lipid peroxidation-PKCβII-ACSL4 positive-feedback axis may provide potential targets for ferroptosis-associated disease treatment.
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