ArticleThe EMBO journal2021
A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- TFEB Antagonizes Cardiac Hypertrophy and Failure by Enhancing Lysosomal Capacity and Mitochondrial Function.Circulation research · 2026Article
- NoxO1 promotes endosome formation and reduces intracellular vesicle processing.Redox biology · 2026Article
- The Effectiveness of Manuka Honey in TreatingmicroPublication biology · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- ATG conjugation-dependent/independent mechanisms underlie lysosomal stress-induced TFEB regulation.The Journal of cell biology · 2025Article
- Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans.PLoS biology · 2025Article
- c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors.Antioxidants (Basel, Switzerland) · 2025Article
- Evolutionary conserved regulation of TFEB stability by the E3 ubiquitin ligase WWP2 modulates response to stressiScience · 2025Article
- Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3.Cell death discovery · 2024Article
- Regulation of Caenorhabditis elegans HLH-30 subcellular localization dynamics: Evidence for a redox-dependent mechanism.Free radical biology & medicine · 2024Article
- PRMT-7/PRMT7 activates HLH-30/TFEB to guard plasma membrane integrity compromised by bacterial pore-forming toxins.Autophagy · 2024Article
- From the regulatory mechanism of TFEB to its therapeutic implications.Cell death discovery · 2024Review
- TMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress.Nature communications · 2024Article
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- Enhancement of lysosome biogenesis as a potential therapeutic approach for neurodegenerative diseases.Neural regeneration research · 2023Article
- C. elegans germ granules sculpt both germline and somatic RNAome.Nature communications · 2023Article
- Review
- The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- TFEB-dependent lysosome biogenesis is required for senescence.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH-30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB/HLH-30 regulation through a cysteine-mediated redox switch. Under stress conditions, TFEB-C212 undergoes oxidation, allowing the formation of intermolecular disulfide bonds that result in TFEB oligomerization. TFEB oligomers display increased resistance to mTORC1-mediated inactivation and are more stable under prolonged stress conditions. Mutation of the only cysteine residue present in HLH-30 (C284) significantly reduced its activity, resulting in developmental defects and increased pathogen susceptibility in worms. Therefore, cysteine oxidation represents a new type of TFEB post-translational modification that functions as a molecular switch to link changes in redox balance with expression of TFEB/HLH-30 target genes.
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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.