ArticleFree radical biology & medicine2020
Alcohol-induced CYP2E1, mitochondrial dynamics and retrograde signaling in human hepatic 3D organoids.
Article in Free radical biology & medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 78 citations in OpenAlex.
- Alcohol and Metabolic Stress Synergize to Dysregulate Mitochondrial Health and Lipid Metabolism; Evidence from a Hepatocyte Spheroid Model.Function (Oxford, England) · 2025Article
- Cytochrome P450 2E1 aggravates DXR-induced myocardial injury through imbalanced mitochondrial OPA1.Cell communication and signaling : CCS · 2025Article
- Research progress in the role of gut microbiota in ethanol metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
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- An Overview of In Vitro Models of Alcohol-Related Hepatocellular Carcinoma.Cancer medicine · 2025Review
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- Development of an alcoholic liver disease model for drug evaluation from human induced pluripotent stem cell-derived liver organoids.Acta biochimica et biophysica Sinica · 2024Article
- Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells.Biochemistry and biophysics reports · 2023Article
- Review
- Evaluation of the efficacy of mitochondrial fission inhibitor (Mdivi-1) using non-alcoholic steatohepatitis (NASH) liver organoids.Frontiers in pharmacology · 2023Article
- Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice.Drug design, development and therapy · 2022Article
- ZIP11 Regulates Nuclear Zinc Homeostasis in HeLa Cells and Is Required for Proliferation and Establishment of the Carcinogenic Phenotype.Frontiers in cell and developmental biology · 2022Article
- Use of standard U-bottom and V-bottom well plates to generate neuroepithelial embryoid bodies.PloS one · 2022Article
- The mitochondrially-localized nucleoside diphosphate kinase D (NME4) is a novel metastasis suppressor.BMC biology · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol toxicity is a significant health problem with ~3 million estimated deaths per year globally. Alcohol is metabolized to the toxic metabolite, acetaldehyde by alcohol dehydrogenase or CYP2E1 in the hepatic tissue, and also induces reactive oxygen species (ROS), which together play a pivotal role in cell and tissue damage. Our previous studies with COS-7 cells transduced with unique human CYP2E1 variants that mostly localize to either microsomes or mitochondria revealed that mitochondrially-localized CYP2E1 drives alcohol toxicity through the generation of higher levels of ROS, which has a consequent effect on cytochrome c oxidase (CcO) and mitochondrial oxidative function. Alcohol treatment of human hepatocyte cell line, HepaRG, in monolayer cultures increased ROS, affected CcO activity/stability, and induced mitophagy. Alcohol treatment of 3D organoids of HepaRG cells induced higher levels of CYP2E1 mRNA and activated mitochondrial stress-induced retrograde signaling, and also induced markers of hepatic steatosis. Knock down of CYP2E1 mRNA using specific shRNA, FK506, a Calcineurin inhibitor, and Mdivi-1, a DRP1 inhibitor, ameliorated alcohol-induced mitochondrial retrograde signaling, and hepatic steatosis. These results for the first time present a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulates the in vivo liver response.
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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.