ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Diallyl Trisulfide From Garlic Regulates RAB18 Phase Separation to Inhibit Lipophagy and Induce Cuproptosis in Hepatic Stellate Cells for Antifibrotic Effects.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis on the safety and efficacy of long-term garlic consumption as an adjunctive treatment for hypertension.Frontiers in nutrition · 2025Pooled it
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Cuproptosis in Ischemic Stroke: Molecular Mechanisms and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- Unravelling the Therapeutic Potential of Cysteine for Cardiovascular Health.International journal of molecular sciences · 2026Review
- The Spatial Redox-Metalloptosis Axis in Liver Disease: A Hypothesis on Regional Susceptibility to Ferroptosis and Cuproptosis.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting mitochondrial-ER homeostasis via autophagy inhibition with celastrol-based nanotherapy for triple-negative breast cancer.Journal of nanobiotechnology · 2026Article
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- DHA Targets RAB1B to Mediate the Driving Force Transmission of Copper Ion Vesicular Endocytosis Under Copper Overload for Promoting Cuproptosis and Ferroptosis in Hepatic Stellate Cells.International journal of biological sciences · 2026Article
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Vitisin A inhibits liver fibrosis by promoting Nrf2/HO-1 pathway and inhibiting Cuproptosis.Scientific reports · 2025Article
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- Cracking the Sulfur Code: Garlic Bioactive Molecules as Multi-Target Blueprints for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- Diallyl Trisulfide From Garlic Regulates RAB18 Phase Separation to Inhibit Lipophagy and Induce Cuproptosis in Hepatic Stellate Cells for Antifibrotic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Liver fibrosis, a common pathological process, severely impacts human health, yet effective treatments are lacking. Cuproptosis, a newly discovered form of cell death induced by copper ions, triggers cytotoxic stress through lipoylated protein oligomerization and may offer a novel therapeutic strategy for liver fibrosis. However, the mechanisms underlying cuproptosis in liver fibrosis are not well understood. During liver fibrosis progression, hepatic stellate cells (HSCs) activate, proliferate, and secrete extracellular matrix components, contributing to fibrosis. Activated HSCs also undergo lipophagy, the degradation of lipid droplets. The study shows that Ras-related protein Rab-18 (RAB18), a protein involved in lipid metabolism, inhibits lipophagy, upregulates Carnitine palmitoyltransferase 1A (CPT1A), and promotes succinylation of dihydrolipoamide dehydrogenase (DLD) at site K320, triggering cuproptosis in HSCs. Diallyl trisulfides (DATs), a garlic-derived compound, induces phase separation of RAB18 and promotes mitochondrial-associated membrane structures (MAMs) formation, further accelerating RAB18 phase separation. DATs selectively protects hepatocytes while activating cuproptosis in HSCs. Interfering with RAB18 expression reverses the DATs-induced inhibition of lipophagy and cuproptosis. These findings, confirmed in primary cells, human liver stellate cells (LX2), rodent models and clinical samples, suggest that DATs, by targeting RAB18 and inducing its phase separation, subsequently inhibit lipophagy and promote cuproptosis, making it a promising therapeutic approach for liver fibrosis. [Correction added on 02 May 2025, after first online publication: In line 4 of the abstract, "sulfenylated" was updated to "lipoylated".].
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.