ArticleMolecular cell2024
Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell death and differentiation · 2026Article
- LKB1 Loss Sensitizes Lung Tumor Spheres to Mitomet-Induced Ferroptosis, and These Effects are Enhanced by mTOR Inhibition.Molecular carcinogenesis · 2026Article
- Proteomic Analysis Reveals AMPKα-Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer.Cancer science · 2026Article
- DHODH-Mediated Suppression of Ferroptosis Supports Radioresistance and Represents a Therapeutic Vulnerability in Lung Cancer.Cancer research · 2026Article
- Ferroptosis as an approach to leverage cancer metabolism.Trends in cell biology · 2026Review
- Elevated labile iron contributes to membrane repair deficits in facioscapulohumeral muscular dystrophy.iScience · 2026Article
- CoQExperimental & molecular medicine · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- GOT2-mediated suppression of CoQCommunications biology · 2026Article
- Review
- Metformin induces ferroptosis associated with lipidomic remodeling in AML.Blood advances · 2026Article
- Mitochondrial LINC00942 activates complex I and inhibits ferroptosis through interacting with GRSF1 in liver cancer.Science China. Life sciences · 2026Article
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- Article
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.
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