Lysosomes, as central organelles of the endolysosomal system, support cell growth by releasing nutrients derived from hydrolytic digestion of macromolecules. Additionally, they serve as storage organelles for ions and amino acids and must respond to changes in osmolarity by adjusting their membrane to maintain membrane integrity. The nutrient-sensing target of rapamycin complex 1 (TORC1) and the lipid kinase Fab1 (PIKfyve in mammals) are key regulators of these processes on yeast vacuoles. TORC1 phosphorylates Fab1, yet how their activities are functionally coupled is unknown. Here, we show that yeast TORC1 is essential for the sorting of Fab1-derived phosphatidylinositol-3,5-bisphosphate (PI(3,5)P₂) from vacuoles to signaling endosomes (SEs), whose formation depends on the CROP membrane remodeling complex. TORC1 phosphorylation activates Fab1, presumably to maintain elevated PI(3,5)P₂ levels on SEs toward cell growth. In mutants defective in endosome-vacuole fusion, PI(3,5)P₂ accumulates on endosomes adjacent to the vacuole, indicating that its hydrolysis primarily occurs on the vacuolar membrane. Our findings reveal that synthesis and spatial distribution of the vacuolar signaling lipid PI(3,5)P₂ are directly coordinated by TORC1, coupling nutrient sensing to membrane remodeling and endosomal signaling.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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