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Nutrient-regulated control of lysosome function by signaling lipid conversion

Lysosomes serve dual antagonistic functions in cells by mediating anabolic growth signaling and the cata-bolic turnover of macromolecules. How these janus-faced activities are regulated in response to cellular nutrient status is poorly understood. We show here that lysosome morphology and function a...

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Main Authors: Ebner, Michael (Author) , Puchkov, Dmytro (Author) , Lopez-Ortega, Orestes (Author) , Muthukottiappan, Pathma (Author) , Su, Yanwei (Author) , Schmied, Christopher (Author) , Zillmann, Silke (Author) , Nikonenko, Iryna (Author) , Koddebusch, Jochen (Author) , Dornan, Gillian L. (Author) , Lucht, Max T. (Author) , Koka, Vonda (Author) , Jang, Wonyul (Author) , Koch, Philipp Alexander (Author) , Wallroth, Alexander (Author) , Lehmann, Martin (Author) , Brügger, Britta (Author) , Pende, Mario (Author) , Winter, Dominic (Author) , Haucke, Volker (Author)
Format: Article (Journal)
Language:English
Published: 22 November 2023
In: Cell
Year: 2023, Volume: 186, Issue: 24, Pages: 5328-5346.e26
ISSN:1097-4172
DOI:10.1016/j.cell.2023.09.027
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2023.09.027
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867423010814?via%3Dihub
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Author Notes:Michael Ebner, Dmytro Puchkov, Orestes Lopez-Ortega, Pathma Muthukottiappan, Yanwei Su, Christopher Schmied, Silke Zillmann, Iryna Nikonenko, Jochen Koddebusch, Gillian L. Dornan, Max T. Lucht, Vonda Koka, Wonyul Jang, Philipp Alexander Koch, Alexander Wallroth, Martin Lehmann, Britta Bruegger, Mario Pende, Dominic Winter, Volker Haucke
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Summary:Lysosomes serve dual antagonistic functions in cells by mediating anabolic growth signaling and the cata-bolic turnover of macromolecules. How these janus-faced activities are regulated in response to cellular nutrient status is poorly understood. We show here that lysosome morphology and function are reversibly controlled by a nutrient-regulated signaling lipid switch that triggers the conversion between peripheral motile mTOR complex 1 (mTORC1) signaling-active and static mTORC1-inactive degradative lysosomes clustered at the cell center. Starvation-triggered relocalization of phosphatidylinositol 4-phosphate (PI(4) P)-metabolizing enzymes reshapes the lysosomal surface proteome to facilitate lysosomal proteolysis and to repress mTORC1 signaling. Concomitantly, lysosomal phosphatidylinositol 3-phosphate (PI(3)P), which marks motile signaling-active lysosomes in the cell periphery, is erased. Interference with this PI(3)P/PI(4) P lipid switch module impairs the adaptive response of cells to altering nutrient supply. Our data unravel a key function for lysosomal phosphoinositide metabolism in rewiring organellar membrane dynamics in response to cellular nutrient status.
Item Description:Gesehen am 16.12.2024
Online veröffentlicht: 25. Oktober 2023
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2023.09.027

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