ArticleProceedings of the National Academy of Sciences of the United States of America2023
The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Exercise-induced lysosomal adaptations in skeletal muscle.Sports medicine and health science · 2026Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- A multi-omic approach reveals iron availability influences cell fate fidelity.npj metabolic health and disease · 2026Article
- AICAr Inhibition of cardiomyocyte autophagy promotes p62-dependent NRF2 expression and protection against doxorubicin toxicity.Cellular and molecular life sciences : CMLS · 2025Article
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.Acta neuropathologica communications · 2025Article
- Feedback Loops Shape Oxidative and Immune Interactions in Hepatic Ischemia-Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Lysosomal-Mitochondrial Interaction Promotes Tumor Growth in Squamous Cell Carcinoma of the Head and Neck.Molecular cancer research : MCR · 2025Article
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Promising tools into oxidative stress: A review of non-rodent model organisms.Redox biology · 2024Review
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Cullin-3 proteins be a novel biomarkers and therapeutic targets for hyperchloremia induced by oral poisoning.Scientific reports · 2024Article
- Review
- Research progresses on mitochondrial-targeted biomaterials for bone defect repair.Regenerative biomaterials · 2024Review
- TAZ deficiency impairs the autophagy-lysosomal pathway through NRF2 dysregulation and lysosomal dysfunction.International journal of biological sciences · 2024Article
- Tanshinlactone triggers methuosis in breast cancer cells via NRF2 activation.Frontiers in pharmacology · 2024Article
- Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.Cells · 2023Article
- Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury.Antioxidants (Basel, Switzerland) · 2023Review
- The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The maintenance of redox and metabolic homeostasis is integral to embryonic development. Nuclear factor erythroid 2-related factor 2 (NRF2) is a stress-induced transcription factor that plays a central role in the regulation of redox balance and cellular metabolism. Under homeostatic conditions, NRF2 is repressed by Kelch-like ECH-associated protein 1 (KEAP1). Here, we demonstrate that Keap1 deficiency induces Nrf2 activation and postdevelopmental lethality. Loss of viability is preceded by severe liver abnormalities characterized by an accumulation of lysosomes. Mechanistically, we demonstrate that loss of Keap1 promotes aberrant activation of transcription factor EB (TFEB)/transcription factor binding to IGHM Enhancer 3 (TFE3)-dependent lysosomal biogenesis. Importantly, we find that NRF2-dependent regulation of lysosomal biogenesis is cell autonomous and evolutionarily conserved. These studies identify a role for the KEAP1-NRF2 pathway in the regulation of lysosomal biogenesis and suggest that maintenance of lysosomal homeostasis is required during embryonic development.
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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 Socratic graph.