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Nutrient regulated control of lysosome function by signaling lipid conversion

ABSTRACT: Lysosomes serve dual antagonistic functions in cells by mediating anabolic growth signaling and the catabolic 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 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 by erasing phosphatidylinositol 3-phosphate [PI(3)P], which marks motile signaling-active lysosomes in the cell periphery. 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Pathma Muthukottiappan

LAB HEAD: Dr.Dominic Winter

PROVIDER: PXD038428 | Pride | 2025-02-10

REPOSITORIES: Pride

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			Action	DRS
	20221014_Haucke_Enriched_lyso_EBSS_R2_DIA.raw	Raw
	20221014_Haucke_Enriched_lyso_PI4K2AKO_R1_DIA.raw	Raw
	20221014_Haucke_Enriched_lyso_PI4K2AKO_R3_DIA.raw	Raw
	20221014_Haucke_Enriched_lyso_WT_R3_DIA.raw	Raw
	20221015_Haucke_Enriched_lyso_EBSS_R1_DIA.raw	Raw

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