ArticleAlcoholism, clinical and experimental research2020
Perturbations in Mitochondrial Dynamics Are Closely Involved in the Progression of Alcoholic Liver Disease.
Article in Alcoholism, clinical and experimental research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease.Scientific reports · 2021Trial
- Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.Biomedical chromatography : BMC · 2026Review
- Microplastics, nanoplastics and liver disease: an emerging health concern?Nature reviews. Gastroenterology & hepatology · 2026Review
- Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis.Journal of advanced research · 2026Article
- Mitochondrial Calcium Signaling in Hepatocyte Health and Disease.Cold Spring Harbor perspectives in biology · 2026Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- Mitofusin 2 is required for preventing deoxynivalenol-induced porcine intestinal epithelial cell damage.Journal of animal science and biotechnology · 2025Article
- Mitochondrial Dysfunction in Endothelial Cells: A Key Driver of Organ Disorders and Aging.Antioxidants (Basel, Switzerland) · 2025Review
- Excessive alcohol consumption: a driver of metabolic dysfunction and inflammation.Frontiers in toxicology · 2025Review
- The Role of Mitochondrial Quality Control in Liver Diseases: Dawn of a Therapeutic Era.International journal of biological sciences · 2025Review
- MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.bioRxiv : the preprint server for biology · 2024Article
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
- GSDMD induces hepatocyte pyroptosis to trigger alcoholic hepatitis through modulating mitochondrial dysfunction.Cell division · 2024Article
- Phosphoglycerate mutase 5 aggravates alcoholic liver disease through disrupting VDAC-1-dependent mitochondrial integrity.International journal of medical sciences · 2024Article
- Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease.International journal of molecular sciences · 2023Article
- Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing.EBioMedicine · 2023Article
- Zonal expression of StARD1 and oxidative stress in alcoholic-related liver disease.Journal of lipid research · 2023Article
- Experimental Models for Studying Structural and Functional State of the Pathological Liver (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation.Cell death & disease · 2022Article
- Review
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundMitochondria play a fundamental role in the pathogenesis of alcoholic liver disease (ALD). The preservation of functional mitochondria during toxic alcohol insults is essential for cell survival and is maintained by key processes known as mitochondrial dynamics, including fragmentation and fusion, which are regulated by mitochondria-shaping proteins (MSP). We have shown mitochondrial dynamics to be distorted by alcohol in cellular and animal models, but the effect in humans remains unknown.
methodsHepatic gene expression of the main MSP involved in the mitochondrial fusion and fragmentation pathways was evaluated in patients with alcoholic hepatitis (AH) by DNA microarray (n = 15) and Reverse Transcription Polymerase Chain Reaction (n = 32). The activation of dynamin-1-like protein (Drp1) was also investigated in mitochondria isolated from liver biopsies of ALD patients (n = 8). The effects of alcohol on mitochondrial dynamics and on MSP protein expression were studied in human precision-cut liver slices (PCLS) exposed for 24 hours to increasing doses of ethanol (EtOH; 50 to 250 mM).
resultsA profound hyperactivation of the fragmentation pathway was observed in AH patients, with a significant increase in the expression of Drp1 and its adapters/receptors. The translocation of Drp1 to the mitochondria was also induced in patients with severe ALD and was affected in the PCLS with short-term exposure to EtOH but only mildly. The fusion pathway was not altered in ALD, and this was confirmed in the PCLS model.
conclusionsThe present study reveals the role of mitochondrial dynamics in human ALD, confirming our previous observations in animal and cell culture models of ALD. Taken together, we show that alcohol has a significant impact on the fragmentation pathway, and we confirm Drp1 as a potential therapeutic target in severe ALD.
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