Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor

Significance The lysosome-like vacuole is the main organelle to degrade membrane proteins and organelles and, thus, provides amino acids, but also ions to the cytosol for cellular survival. Maintenance of vacuole membrane integrity is thus important for cellular adaptations. The vacuole contains several protein complexes on its surface to maintain the vacuole functional, and one such complex is a lipid kinase named Fab1 (of PIKfyve in human cells). Fab1 is part of a protein complex that produces a phosphorylated lipid, PI-3,5-P 2 . Other proteins bind PI-3,5-P 2 and can fragment the vacuole to balance volume vs. membrane during stress. We now identify Ivy1 as a protein that binds Fab1 and controls its activity.