Ion transport as a determinant of membrane fusion and fission

The balance between membrane fusion and fission dictates the size and shape of intracellular organelles: excess fusion causes their enlargement, and predominant fission leads to fragmentation and resorption. These processes are differentially affected by membrane tension. Fusion is favored by increased tension, and the opposite is true for fission. Variations in membrane tension therefore underlie organellar remodeling. In this Review, we analyze the central role of hydrostatic pressure generated by osmotic imbalance in dictating membrane traffic. Using the endocytic pathway as a framework, we describe the predominant role of ions and their transport pathways in establishing intraorganellar osmolarity. We illustrate the role of ion transport regulation in organellar volume homeostasis by analyzing the mechanism underlying the massive vacuolation that results from inhibition of phosphatidylinositol 3,5-bisphosphate synthesis by PIKfyve.