Mitofusin 2: from functions to disease

a The scheme represents the linear structure of MFN2. Note the large N-terminal GTPase domain, followed by the HR1-domain, the PR domain, the two TM domains, and the C-terminal HR2 domain. The numbers above indicate the initial and the terminal amino acids of the corresponding domains. b The cartoon represents MFN2 topology, with two very close TM domains crossing the OMM (green helices) and the indicated cytosolic portions. Note the GTPase domain with two GTP-binding pockets. c Scheme of the OMM-fusion activity of MFNs. Tethering is mediated by the interaction between HR2 domains belonging to MFNs on opposite OMM. Recent data suggest that dimerization of the GTPase domains, as well as a power stroke due to GTP hydrolysis, may be important for fusion (see text for details