Although catalyzed by different proteins, the energy barriers for lipid bil
ayer fusion in exocytosis, viral fusion, and trafficking seem to be the sam
e as those for the fusion of protein-free phospholipid membranes. To minimi
ze this energy, fusion will proceed through a minimal number of lipid molec
ules, probably localized in bent non-bilayer intermediates. Experiments on
phospholipid bilayer membrane fusion show the pathway of contact, hemifusio
n, flickering fusion pore formation, and fusion pore enlargement caused by
swelling of the vesicle. Lipid curvature determines the barriers to hemifus
ion and fusion pore formation, while swelling-induced membrane tension driv
es fusion pore enlargement. Experiments on viral protein-induced cell-cell
fusion and exocytosis show the same pathway with the same fundamental effec
ts of lipid curvature and membrane tension. Thus while proteins control the
se reactions, lipid energetics determine the basic reaction scheme for memb
rane fusion. Published by Elsevier Science B.V.