ArticleCell reports2020
A FLCN-TFE3 Feedback Loop Prevents Excessive Glycogenesis and Phagocyte Activation by Regulating Lysosome Activity.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- Folliculin Deletion in the Mouse Kidney Results in Cystogenesis of the Loops of Henle via Aberrant TFEB Activation.The American journal of pathology · 2025Article
- Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.International journal of molecular sciences · 2024Review
- PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis.Human molecular genetics · 2023Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Article
- Lysophosphatidylcholine Alleviates Acute Lung Injury by Regulating Neutrophil Motility and Neutrophil Extracellular Trap Formation.Frontiers in cell and developmental biology · 2022Article
- Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways.Scientific reports · 2021Article
- Interleukin-27 promotes autophagy in human serum-induced primary macrophages via an mTOR- and LC3-independent pathway.Scientific reports · 2021Article
- Mitochondria Turnover and Lysosomal Function in Hematopoietic Stem Cell Metabolism.International journal of molecular sciences · 2021Review
- YAP plays a crucial role in the development of cardiomyopathy in lysosomal storage diseases.The Journal of clinical investigation · 2021Article
- Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells.eLife · 2021Article
- Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways.Frontiers in cell and developmental biology · 2021Review
- Article
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
The tumor suppressor folliculin (FLCN) suppresses nuclear translocation of TFE3, a master transcription factor for lysosomal biogenesis, via regulation of amino-acid-sensing Rag GTPases. However, the importance of this lysosomal regulation in mammalian physiology remains unclear. Following hematopoietic-lineage-specific Flcn deletion in mice, we found expansion of vacuolated phagocytes that accumulate glycogen in their cytoplasm, phenotypes reminiscent of lysosomal storage disorder (LSD). We report that TFE3 acts in a feedback loop to transcriptionally activate FLCN expression, and FLCN loss disrupts this loop, augmenting TFE3 activity. Tfe3 deletion in Flcn knockout mice reduces the number of phagocytes and ameliorates LSD-like phenotypes. We further reveal that TFE3 stimulates glycogenesis by promoting the expression of glycogenesis genes, including Gys1 and Gyg, upon loss of Flcn. Taken together, we propose that the FLCN-TFE3 feedback loop acts as a rheostat to control lysosome activity and prevents excessive glycogenesis and LSD-like phagocyte activation.
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Registered trials
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