Mitofusin 2: A Mitochondria-Shaping Protein with Signaling Roles Beyond Fusion

Mitochondria are central organelles in metabolism, signal transduction, and programmed cell death. To meet their diverse functional demands, their shape is strictly regulated by a growing family of proteins that impinge on fission and fusion of the organelle. Mitochondrial fusion depends on Mitofusin (Mfn) 1 and 2, two integral outer-membrane proteins. Although MFN1 seems primarily involved in the regulation of the docking and fusion of the organelle, mounting evidence is implicating MFN2 in multiple signaling pathways not restricted to the regulation of mitochondrial shape. Here we review data supporting a role for this mitochondria-shaping protein beyond fusion, in regulating mitochondrial metabolism, apoptosis, shape of other organelles, and even progression through cell cycle. In conclusion, MFN2 appears a multifunctional protein whose biologic function is not restricted to the regulation of mitochondrial shape.