FLCN Regulates Transferrin Receptor 1 Transport and Iron Homeostasis

January 2021 in “ Journal of biological chemistry/The Journal of biological chemistry ”

Xiaojuan Wang, Huawei Wu, Lingling Zhao, Zeyao Liu, Maozhen Qi, Yaping Jin, Wei Liu

folliculin transferrin receptor 1 iron homeostasis Rab11A hypoxia-inducible factor iron uptake iron deficiency iron supplementation Birt-Hogg-Dubé syndrome FLCN TfR1 HIF BHD syndrome

Studysummary This study found that loss of the folliculin protein delays transferrin receptor recycling, leading to iron deficiency and suggesting a role in the mechanisms of Birt-Hogg-Dubé syndrome.

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The study investigated the role of folliculin (FLCN) in regulating transferrin receptor 1 (TfR1) transport and iron homeostasis using human kidney-derived HEK293 cells and a Drosophila model. FLCN promoted the binding of Rab11A with TfR1, essential for iron uptake. Loss of FLCN disrupted this interaction, delaying TfR1 recycling and causing iron deficiency, which activated hypoxia-inducible factor (HIF) activity. Iron supplementation reversed these effects. In Drosophila, an iron-rich diet rescued the phenotype of BHD mutant larvae. These findings highlighted FLCN's conserved function in iron metabolism and provided insights into Birt-Hogg-Dubé (BHD) syndrome mechanisms.

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Research cited in this study

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research Regulation of Mitochondrial Oxidative Metabolism by Tumor Suppressor FLCN

81 citations , November 2012 in “Journal of the National Cancer Institute”

This study found that FLCN deficiency in mice muscles led to increased mitochondrial biogenesis and a metabolic shift towards oxidative phosphorylation, with a similar advantage observed in FLCN-null kidney cancer cells.

research Folliculin Encoded by the BHD Gene Interacts with a Binding Protein, FNIP1, and AMPK, and Is Involved in AMPK and mTOR Signaling

475 citations , October 2006 in “Proceedings of the National Academy of Sciences”

This study suggests that folliculin, mutated in Birt–Hogg–Dubé syndrome, and its partner FNIP1 may play a role in energy and nutrient sensing through the AMPK and mTOR pathways.