Mitofusin-1 (MFN1)

Mitofusin-1 (MFN1) is a mitochondrial outer membrane GTPase essential for the process of mitochondrial fusion and maintenance of mitochondrial network morphology[3][4]. Along with its paralog mitofusin-2 (MFN2), it mediates the tethering and subsequent fusion of the outer membranes of adjacent mitochondria through GTP-dependent oligomerization and conformational changes[1][2][4]. Structurally, MFN1 contains an N-terminal GTPase domain, a transmembrane domain that anchors it in the outer mitochondrial membrane, and two heptad repeat coiled-coil domains (HR1 and HR2) critical for membrane tethering and fusion[1][2][4]. By regulating mitochondrial morphology, MFN1 influences important cellular processes such as energy production, apoptosis, cell proliferation, and signaling[1][2][3][4]. Both loss and gain of MFN1 function are linked to pathological conditions including neurodegenerative disorders and cardiovascular disease, highlighting its role as a potential therapeutic target[2][4][5]. Small molecules such as MASM7 have been identified that can activate MFN1, promoting mitochondrial fusion, serving as potential tools for modulating mitochondrial dynamics in disease contexts[2].

Other names

Mitofusin-1MFN1Fzo homologTransmembrane GTPase MFN1hfzo1hfzo2mitochondrial transmembrane GTPase FZO-2mitochondrial transmembrane GTPase Fzo-1putative transmembrane GTPaseFLJ20693

Activation or inhibition of mitochondrial fusion via direct modulation of MFN1 oligomerization and conformational state[2]