ArticleNature communications2024
Inhibition of 7-dehydrocholesterol reductase prevents hepatic ferroptosis under an active state of sterol synthesis.
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 38 papers.
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Who cites it
38 citing papers in PubMed.
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Ferroptotic propagation: from single-cell execution to tissue-scale death programs.Cell research · 2026Review
- Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress.The Journal of cell biology · 2026Article
- MESH1-mediated coenzyme A degradation drives ferroptosis sensitivity and muscle pathology.The Journal of clinical investigation · 2026Article
- An inflammation-targeted lipid nanoparticle inhibiting ferroptosis for spinal cord injury repair.Materials today. Bio · 2026Article
- Ascites protects against ferroptosis and enables the peritoneal growth of ovarian cancer.Nature communications · 2026Article
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- Declined RTN3 stabilizes DHCR7 to induce cholesterol-dependent tumor progression and MEK inhibitors insensitivity in thyroid cancer.Cell death & disease · 2026Article
- Modeling Microbiome Modulation of Tumor Metabolic Networks to Predict Synergistic Therapies.bioRxiv : the preprint server for biology · 2026Article
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- Ferroptosis: unveiling a transformative perspective in the landscape of autoimmune diseases.Frontiers in immunology · 2026Review
- Hormetic Effects of 7-Ketocholesterol in Preventing Ferroptosis in Hepatocytes.Oxidative medicine and cellular longevity · 2026Article
- Ferroptosis in metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2026Review
- Metabolic control of ferroptosis in cancer: lipid dependencies as therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- The impact of lipid metabolism on ferroptosis in myocardial ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2025Review
- Decoding ferroptosis for cancer therapy.Nature reviews. Cancer · 2025Review
- Ferroptosis: biology and role in liver disease.Journal of gastroenterology · 2025Review
- FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis.Nature cell biology · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, the organ-specific regulation mechanism is poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), the terminal enzyme of cholesterol biosynthesis, as a regulator of ferroptosis in hepatocytes. Genetic and pharmacological inhibition (with AY9944) of DHCR7 suppress ferroptosis in human hepatocellular carcinoma Huh-7 cells. DHCR7 inhibition increases its substrate, 7-dehydrocholesterol (7-DHC). Furthermore, exogenous 7-DHC supplementation using hydroxypropyl β-cyclodextrin suppresses ferroptosis. A 7-DHC-derived oxysterol metabolite, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), is increased by the ferroptosis-inducer RSL-3 in DHCR7-deficient cells, suggesting that the ferroptosis-suppressive effect of DHCR7 inhibition is associated with the oxidation of 7-DHC. Electron spin resonance analysis reveals that 7-DHC functions as a radical trapping agent, thus protecting cells from ferroptosis. We further show that AY9944 inhibits hepatic ischemia-reperfusion injury, and genetic ablation of Dhcr7 prevents acetaminophen-induced acute liver failure in mice. These findings provide new insights into the regulatory mechanism of liver ferroptosis and suggest a potential therapeutic option for ferroptosis-related liver diseases.
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