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Membrane fusion reactions consist of three steps: close apposition of membranes, mixing of lipid molecules, and formation of new bilayers in a different direction. For elucidation of the molecular mechanisms of these three steps, we have studied membrane fusion induced by amphipathic helical peptides and the protein clathrin using liposome membrane systems. Based on the results, we propose two different mechanisms of membrane close apposition: close apposition of negatively or positively charged membranes occurs through the hydrophobic interaction between proteins or peptides after their electrostatic binding to the membranes, whereas close apposition of neutral membranes occurs through the membrane binding and self-aggregative properties of proteins or peptides that are provided by neutralization of their surface charges. We also propose a possible mechanism for the lipid-mixing reaction to form new bilayers, which is interpreted in terms of destabilization of the bilayer structure within hydrophobic protein- or peptide-membrane assemblies and stabilization of the bilayer structure in their hydrophilic media. [ABSTRACT FROM AUTHOR]