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Nutrient-regulated control of lysosome function by signaling lipid conversion
Cited 4 time in
Web of Science
Cited 9 time in Scopus
- Authors
- Issue Date
- 2023-11
- Publisher
- CELL PRESS
- Citation
- CELL, Vol.186 No.24, pp.5328-+
- Abstract
- 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.
- ISSN
- 0092-8674
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