ArticleThe Journal of biological chemistry2013
Human cytochrome P450 2E1 mutations that alter mitochondrial targeting efficiency and susceptibility to ethanol-induced toxicity in cellular models.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Unraveling the Role of CYP2E1 in Antitubercular Drug-Induced Hepatotoxicity: From Molecular Mechanisms to Clinical Implications.International journal of hepatology · 2025Review
- 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
- Subcellular expression of CYP2E1 in HepG2 cells impacts response to free oleic and palmitic acid.Current research in toxicology · 2024Article
- The Synergistic and Opposing Roles of ω-Fatty Acid Hydroxylase (Genome biology & molecular genetics · 2024Article
- CYP2E1 overexpression protects COS-7 cancer cells against ferroptosis.Research square · 2023Article
- Review
- Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Review
- Alcohol-induced CYP2E1, mitochondrial dynamics and retrograde signaling in human hepatic 3D organoids.Free radical biology & medicine · 2020Article
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
- β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP⁺ Toxicity in Human Neuroblastoma SH-SY5Y Cells.International journal of molecular sciences · 2018Article
- The relationships between cytochromes P450 and HJournal of inorganic biochemistry · 2018Review
- Activation of autophagy attenuates EtOH-LPS-induced hepatic steatosis and injury through MD2 associated TLR4 signaling.Scientific reports · 2017Article
- 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice.Toxicology · 2017Article
- Toxicological Implications of Mitochondrial Localization of CYP2E1.Toxicology research · 2017Article
- Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances.Current molecular pharmacology · 2017Review
- A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen.Toxicology and applied pharmacology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human polymorphisms in the 5'-upstream regulatory regions and also protein coding regions of cytochrome P450 2E1 (CYP2E1) are known to be associated with several diseases, including cancer and alcohol liver toxicity. In this study, we report novel mutations in the N-terminal protein targeting regions of CYP2E1 that markedly affect subcellular localization of the protein. Variant W23R/W30R protein (termed W23/30R) is preferentially targeted to mitochondria but very poorly to the endoplasmic reticulum, whereas the L32N protein is preferentially targeted to the endoplasmic reticulum and poorly to mitochondria. These results explain the physiological significance of bimodal CYP targeting to the endoplasmic reticulum and mitochondria previously described. COS-7 cells and HepG2 cells stably expressing W23/30R mutations showed markedly increased alcohol toxicity in terms of increased production of reactive oxygen species, respiratory dysfunction, and loss of cytochrome c oxidase subunits and activity. Stable cells expressing the L32N variant, on the other hand, were relatively less responsive to alcohol-induced toxicity and mitochondrial dysfunction. These results further support our previous data, based on mutational studies involving altered targeting, indicating that mitochondria-targeted CYP2E1 plays an important role in alcohol liver toxicity. The results also provide an interesting new link to genetic variations affecting subcellular distribution of CYP2E1 with alcohol-induced toxicity.
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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.