Mitofusin-2 (MFN2)

Mitofusin-2 (MFN2) is a dynamin-like GTPase located in the outer mitochondrial membrane that is essential for mitochondrial fusion, modulating mitochondrial morphology, distribution, and bioenergetics. It forms oligomers via its GTPase and coiled-coil domains to bridge adjacent mitochondria and promote their fusion. MFN2 also regulates contacts between the endoplasmic reticulum and mitochondria (ER-mitochondria tethering), plays roles in mitochondrial trafficking (notably in neurons), and is involved in critical processes such as apoptosis, autophagy, and maintenance of cellular energy homeostasis. Mutations in MFN2 are causative for Charcot-Marie-Tooth disease type 2A, and alterations in its expression and function are implicated in cardiovascular diseases, cancer, and metabolic disorders[1][2][3][4][5][6]. No selective clinical drugs directly targeting MFN2 are yet available, though preclinical molecules that affect mitochondrial fusion are in early stages of investigation. Dysregulation or inhibition of MFN2 can cause severe toxicity in energy-dependent tissues, presenting a safety consideration for therapeutic targeting.

Other names

MFN2Transmembrane GTPase MFN2Fuzzy onions homolog 2Mfn-2

Promotion or inhibition of mitochondrial fusion by modulating MFN2’s GTPase activity or protein-protein interactions; Modulation of ER-mitochondria tethering; Regulation of mitochondrial quality control pathways (e.g., mitophagy, apoptosis)