ArticlePloS one2016
FLCN Maintains the Leucine Level in Lysosome to Stimulate mTORC1.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- High Concentration of FBS Can Save mTOR Down-Regulation Caused byVeterinary sciences · 2022Article
- PAT2 regulates vATPase assembly and lysosomal acidification in brown adipocytes.Molecular metabolism · 2022Article
- Molecular mechanisms of dietary restriction promoting health and longevity.Nature reviews. Molecular cell biology · 2022Review
- Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Review
- Lysosomes in T Cell Immunity and Aging.Frontiers in aging · 2021Review
- A GC-MS/Single-Cell Method to Evaluate Membrane Transporter Substrate Specificity and Signaling.Frontiers in molecular biosciences · 2021Article
- Regulation of Body Size and Growth Control.Genetics · 2020Review
- The Lysosome Signaling Platform: Adapting With the Times.Frontiers in cell and developmental biology · 2019Review
- Lysosome: The metabolic signaling hub.Traffic (Copenhagen, Denmark) · 2019Review
- Regulation of metabolic health by essential dietary amino acids.Mechanisms of ageing and development · 2019Review
- mTORC1 and Nutrient Homeostasis: The Central Role of the Lysosome.International journal of molecular sciences · 2018Review
- mTORC1 as the main gateway to autophagy.Essays in biochemistry · 2017Review
- FLCN regulates transferrin receptor 1 transport and iron homeostasis.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular amino acid pool within lysosome is a signal that stimulates the nutrient-sensing mTORC1 signalling pathway. The signal transduction cascade has garnered much attention, but little is known about the sequestration of the signalling molecules within the lysosome. Using human HEK293 cells as a model, we found that suppression of the BHD syndrome gene FLCN reduced the leucine level in lysosome, which correlated with decreased mTORC1 activity. Both consequences could be reversed by supplementation with high levels of leucine, but not other tested amino acids. Conversely, overexpressed FLCN could sequester lysosomal leucine and stimulate mTORC1 in an amino acid limitation environment. These results identify a novel function of FLCN: it controls mTORC1 by modulating the leucine signal in lysosome. Furthermore, we provided evidence that FLCN exerted this role by inhibiting the accumulation of the amino acid transporter PAT1 on the lysosome surface, thereby maintaining the signal level within the organelle.
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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 OpenQuestion graph.