ArticleCell death & disease2024
Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed.
- NRF2/SLC7A11/GPX4 Antioxidant Axis Suppression by Camel Milk Whey Protein Sensitizes MCF-7 Breast Cancer Cells to Cisplatin.International journal of molecular sciences · 2026Article
- Valproic Acid Inhibits Ferroptosis and Improves Bone Integration in OVX Rats Through the AMPK/SIRT1 Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Double-bond geometry determines fatty acid metabolic fate and ferroptosis sensitivity.bioRxiv : the preprint server for biology · 2026Article
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Interconnected cell death pathways: central mechanisms and therapeutic targets in impaired follicular development of polycystic ovary syndrome.Journal of ovarian research · 2026Review
- Chaperone-Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Repurposing dronedarone induces ferroptosis through GPX4 inactivation and degradation in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Tocotrienols exhibit superior ferroptosis inhibition over tocopherols.Scientific reports · 2026Article
- Review
- Ferroptosis regulation in doxorubicin-induced cardiotoxicity: multi-mechanism interventions and translational strategies.Frontiers in pharmacology · 2026Review
- Sufentanil attenuates LPS-induced acute lung injury by suppressing ferroptosis and maintaining GPX4 protein abundance.Frontiers in cell and developmental biology · 2026Article
- Silencing of telomerase RNA component induces autophagy and ferroptosis in A549 and H838 lung cancer cells via AMPK-mediated signaling.Molecular and cellular biochemistry · 2026Article
- Analytical Determination of the Lipid Fraction ofMolecules (Basel, Switzerland) · 2025Article
- FBXO22 Suppresses Oxidative Stress-Induced ASK1 Activation and Cell Death via Ubiquitination-Dependent Degradation of TRIM48.International journal of molecular sciences · 2025Article
- Lead binds HIF-1α contributing to depression-like behaviour through modulating mitochondria-associated astrocyte ferroptosis.Communications biology · 2025Article
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
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Authors and funding
18 authors.
Funding
Abstract
Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA). CFAs, such as (10E,12Z)-octadecadienoic acid and α-eleostearic acid (ESA), induced GPX4 degradation, generation of mitochondrial reactive oxygen species (ROS) and lipid peroxides, and ultimately ferroptosis in cancer cell lines, including HT1080 and A549 cells, which were suppressed by either pharmacological blockade of CMA or genetic deletion of LAMP2A, a crucial molecule for CMA. Mitochondrial ROS were sufficient and necessary for CMA-dependent GPX4 degradation. Oral administration of an ESA-rich oil attenuated xenograft tumor growth of wild-type, but not that of LAMP2A-deficient HT1080 cells, accompanied by increased lipid peroxidation, GPX4 degradation and cell death. Our study establishes mitochondria as the key target of CFAs to trigger lipid peroxidation and GPX4 degradation, providing insight into ferroptosis-based cancer therapy.
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