ArticleMolecular and cellular biology2014
Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- Empagliflozin Alleviates Hepatic Steatosis and Oxidative Stress via the NRF1 Pathway in High-Fat Diet-Induced Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2025Article
- NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein.Scientific reports · 2025Article
- Research progress of cysteine transporter SLC7A11 in endocrine and metabolic diseases.Molecular biology reports · 2025Review
- NFE2L1 as a central regulator of proteostasis in neurodegenerative diseases: interplay with autophagy, ferroptosis, and the proteasome.Frontiers in molecular neuroscience · 2025Review
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
- NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.Antioxidants (Basel, Switzerland) · 2024Article
- Protective Effects of Hepatocyte Stress Defenders, Nrf1 and Nrf2, against MASLD Progression.International journal of molecular sciences · 2024Article
- Understanding the Transcription Factor NFE2L1/NRF1 from the Perspective of Hallmarks of Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.Cancer medicine · 2024Article
- Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.Frontiers in immunology · 2024Article
- Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.Redox biology · 2023Article
- Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes.Scientific reports · 2023Article
- AKT activation because of PTEN loss upregulates xCT via GSK3β/NRF2, leading to inhibition of ferroptosis in PTEN-mutant tumor cells.Cell reports · 2023Article
- An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.Science advances · 2023Article
- N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.Journal of inherited metabolic disease · 2023Article
- A novel nonsense variant in the NFE2L1 transcription factor in a patient with developmental delay, hypotonia, genital anomalies, and failure to thrive.Human mutation · 2022Article
- Article
- The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Differential Yet Integral Contributions of Nrf1 and Nrf2 in the Human HepG2 Cells on Antioxidant Cytoprotective Response againstAntioxidants (Basel, Switzerland) · 2021Article
- Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Liver-specific Nrf1 (NF-E2-p45-related factor 1) knockout mice develop nonalcoholic steatohepatitis. To identify postnatal mechanisms responsible for this phenotype, we generated an inducible liver-specific Nrf1 knockout mouse line using animals harboring an Nrf1(flox) allele and a rat CYP1A1-Cre transgene (Nrf1(flox/flox)::CYP1A1-Cre mice). Administration of 3-methylcholanthrene (3-MC) to these mice (Nrf1(flox/flox)::CYP1A1-Cre+3MC mice) resulted in loss of hepatic Nrf1 expression. The livers of mice lacking Nrf1 accumulated lipid, and the hepatic fatty acid (FA) composition in such animals differed significantly from that in the Nrf1(flox/flox)::CYP1A1-Cre control. This change was provoked by upregulation of several FA metabolism genes. Unexpectedly, we also found that the level of glutathione was increased dramatically in livers of Nrf1(flox/flox)::CYP1A1-Cre+3MC mice. While expression of glutathione biosynthetic enzymes was unchanged, xCT, a component of the cystine/glutamate antiporter system x(c)(-), was significantly upregulated in livers of Nrf1(flox/flox)::CYP1A1-Cre+3MC mice, suggesting that Nrf1 normally suppresses xCT. Thus, stress-inducible expression of xCT is a two-step process: under homeostatic conditions, Nrf1 effectively suppresses nonspecific transactivation of xCT, but when cells encounter severe oxidative/electrophilic stress, Nrf1 is displaced from an antioxidant response element (ARE) in the gene promoter while Nrf2 is recruited to the ARE. Thus, Nrf1 controls both the FA and the cystine/cysteine content of hepatocytes by participating in an elaborate regulatory network.
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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.