Mitochondrial outer membrane fusion is regulated by several mechanisms. For example, the lipid composition of the mitochondrial outer membrane is important; in particular phosphatidic acid promotes mitochondrial fusion. In addition, the mitofusin proteins can be covalently modified by phosphorylation, acetylation, or ubiquitination. We are currently characterizing the function of phosphorylation sites in the GTPase domain. There are also several proteins that reside in the cytosol or outer membrane that regulate mitofusion activity. We have characterized the role of cytosolic Bax in regulation of Mfn2 and our data indicate that Bax promotes GTP-dependent assembly and improves fusion activity of disease-associated variants. We are also interested in understanding other proteins that regulate mitofusin activity.