ArticleThe Journal of biological chemistry2010
Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 115 citations in OpenAlex.
- AlteredeNeuro · 2026Article
- Article
- Perfluorooctane sulfonate exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- m5C-modified circRREB1 promotes lung cancer progression by inducing mitophagy.Journal of experimental & clinical cancer research : CR · 2025Article
- Cytochrome P450 2E1 aggravates DXR-induced myocardial injury through imbalanced mitochondrial OPA1.Cell communication and signaling : CCS · 2025Article
- Unraveling the Role of CYP2E1 in Antitubercular Drug-Induced Hepatotoxicity: From Molecular Mechanisms to Clinical Implications.International journal of hepatology · 2025Review
- Molecular Subtypes based on Mitochondrial Oxidative Stress-related Gene Signature and Tumor Microenvironment Infiltration Characterization of Colon Adenocarcinoma.Current medicinal chemistry · 2025Article
- Transgenic expression of human cytochrome P450 2E1 in C. elegans and rat PC-12 cells sensitizes to ethanol-induced locomotor and mitochondrial effects.Biochemical and biophysical research communications · 2024Article
- The Synergistic and Opposing Roles of ω-Fatty Acid Hydroxylase (Genome biology & molecular genetics · 2024Article
- Subcellular expression of CYP2E1 in HepG2 cells impacts response to free oleic and palmitic acid.Current research in toxicology · 2024Article
- Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections.International journal of molecular sciences · 2023Review
- Review
- Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Treatment with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and diabetic liver pathology.Frontiers in endocrinology · 2022Article
- CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload.International journal of molecular sciences · 2021Review
- The Placenta as a Target for Alcohol During Pregnancy: The Close Relation with IGFs Signaling Pathway.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism.Food & nutrition research · 2021Article
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The ethanol-inducible cytochrome P450 2E1 (CYP2E1) is also induced under different pathological and physiological conditions. Studies including ours have shown that CYP2E1 is bimodally targeted to both the endoplasmic reticulum (microsomes) (mc CYP2E1) and mitochondria (mt CYP2E1). In this study we investigated the role of mtCYP2E1 in ethanol-mediated oxidative stress in stable cell lines expressing predominantly mt CYP2E1 or mc CYP2E1. The ER+ mutation (A2L, A9L), which increases the affinity of the nascent protein for binding to the signal recognition particle, preferentially targets CYP2E1 to the endoplasmic reticulum. The Mt+ (L17G) and Mt++ (I8R, L11R, L17R) mutant proteins, showing progressively lower affinity for signal recognition particle binding, were targeted to mitochondria at correspondingly higher levels. The rate of GSH depletion, used as a measure of oxidative stress, was higher in cells expressing Mt++ and Mt+ proteins as compared with cells expressing ER+ protein. In addition, the cellular level of F(2)-isoprostanes, a direct indicator of oxidative stress, was increased markedly in Mt++ cells after ethanol treatment. Notably, expression of Mt++ CYP2E1 protein in yeast cells caused more severe mitochondrial DNA damage and respiratory deficiency than the wild type or ER+ proteins as tested by the inability of cells to grow on glycerol or ethanol. Additionally, liver mitochondria from ethanol-fed rats containing high mt CYP2E1 showed higher levels of F(2)-isoprostane production. These results strongly suggest that mt CYP2E1 induces oxidative stress and augments alcohol-mediated cell/tissue injury.
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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.