ArticlePLoS genetics2015
FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen Stores.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 57 citations in OpenAlex.
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- High-throughput behavioural phenotyping of 25 C. elegans disease models including patient-specific mutations.BMC biology · 2025Article
- Shaker/Kv1 potassium channel SHK-1 protects against pathogen infection and oxidative stress in C. elegans.PLoS genetics · 2025Article
- A comprehensive approach, based on the use ofCurrent research in food science · 2025Article
- Regulation of Caenorhabditis elegans HLH-30 subcellular localization dynamics: Evidence for a redox-dependent mechanism.Free radical biology & medicine · 2024Article
- Increased expression of metabolism and lysosome-associated genes in amicroPublication biology · 2024Article
- Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans.Nature communications · 2023Article
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- Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans.Nature communications · 2022Article
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- AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3.Autophagy · 2021Article
- Folliculin impairs breast tumor growth by repressing TFE3-dependent induction of the Warburg effect and angiogenesis.The Journal of clinical investigation · 2021Article
- Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways.Scientific reports · 2021Article
- Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways.Frontiers in cell and developmental biology · 2021Review
- Article
- A metabolic switch regulates the transition between growth and diapause in C. elegans.BMC biology · 2020Article
- FLCN alteration drives metabolic reprogramming towards nucleotide synthesis and cyst formation in salivary gland.Biochemical and biophysical research communications · 2020Article
- A FLCN-TFE3 Feedback Loop Prevents Excessive Glycogenesis and Phagocyte Activation by Regulating Lysosome Activity.Cell reports · 2020Article
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Authors and funding
12 authors at 3 institutions in 4 countries.
Funding
Abstract
Mechanisms of adaptation to environmental changes in osmolarity are fundamental for cellular and organismal survival. Here we identify a novel osmotic stress resistance pathway in Caenorhabditis elegans (C. elegans), which is dependent on the metabolic master regulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN). FLCN-1 is the nematode ortholog of the tumor suppressor FLCN, responsible for the Birt-Hogg-Dubé (BHD) tumor syndrome. We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress via constitutive AMPK-dependent accumulation of glycogen reserves. Upon hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a significant accumulation of the organic osmolyte glycerol through transcriptional upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2). Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies show for the first time that animals normally exhibit AMPK-dependent glycogen stores, which can be utilized for rapid adaptation to either energy stress or hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys from mice lacking FLCN and in renal tumors from a BHD patient. Our findings suggest a dual role for glycogen, acting as a reservoir for energy supply and osmolyte production, and both processes might be supporting tumorigenesis.
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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.