Schematic of revised Mfn topology. (A) Mfns are characterized by a GTPase, a coiled-coil (HR1), and a proline-rich (PR) domain (heptad repeats; HR) facing the cytosol, a transmembrane domain spanning the OMM, and a second coiled-coil (HR) C-terminal domain protruding into the IMS. The cysteine residues sensitive to changes in ROS also face the IMS. (B) Oligomerization of Mfns occurs through the formation of disulphide bridges. Whether Mfn partners with itself or with a yet-undiscovered protein (protein X) to mediate mitochondria docking in trans, necessary for fusion to occur, remains to be defined.