Organelle size control: Accumulating vacuole content activates SNAREs to augment organelle volume by homotypic fusion

Abstract

Cells control the size of their compartments relative to cell volume but there is also size control within each organelle. Yeast vacuoles neither burst nor do they collapse into a ruffled morphology, indicating that the volume of the organellar envelope is adjusted to the amount of content. It is poorly understood how this adjustment is achieved. We show that accumulating content of yeast vacuoles activates fusion of several organelle copies, thus increasing the volume-to-surface ratio. Synthesis of the dominant compound stored inside vacuoles, polyphosphate, stimulates binding of the chaperone Sec18/NSF to vacuolar SNAREs, which activates them and triggers fusion. SNAREs can only be activated by lumenal but not by cytosolic polyphosphate. Control of lumenal polyP over SNARE activation in the cytosol requires the cytosolic cyclin-dependent kinase Pho80/Pho85 and the R-SNARE Nyv1. These results suggest that cells may adapt the volume of vacuoles to their content by feed-back from the vacuole lumen to the SNAREs on the cytosolic surface of the organelle.