ArticleThe Journal of biological chemistry2002
Bimodal targeting of microsomal CYP2E1 to mitochondria through activation of an N-terminal chimeric signal by cAMP-mediated phosphorylation.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 144 citations in OpenAlex.
- 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
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Review
- Oxytocin promotes hepatic regeneration in elderly mice.iScience · 2021Article
- The Placenta as a Target for Alcohol During Pregnancy: The Close Relation with IGFs Signaling Pathway.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Alcohol-induced CYP2E1, mitochondrial dynamics and retrograde signaling in human hepatic 3D organoids.Free radical biology & medicine · 2020Article
- The S100B Protein and Partners in Adipocyte Response to Cold Stress and Adaptive Thermogenesis: Facts, Hypotheses, and Perspectives.Biomolecules · 2020Review
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
- Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression.Hepatology (Baltimore, Md.) · 2019Article
- Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects.Biomedicines · 2018Review
- Age-Related Changes in Expression and Activity of Human Hepatic Mitochondrial Glutathione Transferase Zeta1.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Increased ethanol-inducible cytochrome P450-2E1 and cytochrome P450 isoforms in exosomes of alcohol-exposed rodents and patients with alcoholism through oxidative and endoplasmic reticulum stress.Hepatology communications · 2017Article
- 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice.Toxicology · 2017Article
- Article
- Toxicological Implications of Mitochondrial Localization of CYP2E1.Toxicology research · 2017Article
- Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer's Disease.Oxidative medicine and cellular longevity · 2016Review
- The Localization of Cytochrome P450s CYP1A1 and CYP1A2 into Different Lipid Microdomains Is Governed by Their N-terminal and Internal Protein Regions.The Journal of biological chemistry · 2015Article
- Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates.Toxicology · 2015Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cytochrome P450 2E1 (CYP2E1) plays an important role in alcohol-induced toxicity and oxidative stress. Recently, we showed that this predominantly microsomal protein is also localized in rat hepatic mitochondria. In this report, we show that the N-terminal 30 amino acids of CYP2E1 contain a chimeric signal for bimodal targeting of the apoprotein to endoplasmic reticulum (ER) and mitochondria. We demonstrate that the cryptic mitochondrial targeting signal at sequence 21-31 of the protein is activated by cAMP-dependent phosphorylation at Ser-129. S129A mutation resulted in lower affinity for binding to cytoplasmic Hsp70, mitochondrial translocases (TOM40 and TIM44) and reduced mitochondrial import. S129A mutation, however, did not affect the extent of binding to the signal recognition particle and association with ER membrane translocator protein Sec61. Addition of saturating levels of signal recognition particle caused only a partial inhibition of CYP2E1 translation under in vitro conditions, and saturating levels of ER resulted only in partial membrane integration. cAMP enhanced the mitochondrial CYP2E1 (referred to as P450MT5) level but did not affect its level in the ER. Our results provide new insights on the mechanism of cAMP-mediated activation of a cryptic mitochondrial targeting signal and regulation of P450MT5 targeting to mitochondria.
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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.