Heptad repeat regions of coiled-coil domains of Mfn1 are crucial for Mfn1 mediated mitochondrial fusion

Abstract

Mitofusin mediate fusion of outer mitochondrial membranes (OMM). Recent studies have explained the role of GTPase domain for Mfn1 dimerization and outer mitochondrial membrane (OMM) fusion. Coiled-coiled domains [namely, coiled-coil/Middle domains (CC1MD) and coiled-coil-2 GTPase effector domain (CC2/GED)] form helical bundles that mediate open-to-close conformations of Mfn1 upon GTP binding and have been previously reported to be important for OMM tethering and OMM fusion. To further decipher the significance of helical structure of MD, we functionally characterized the heptad repeat regions of MD. Consistent with previous studies, we show that MD consists of two heptad repeats (HR1, namely HR1a and HR1b) and both of these are crucial for Mfn1 mediated OMM fusion.\n\nHIGHLIGHTSO_LICoiled-coil1 (also known as Middle domain, MD) contains two heptad repeat regions.\nC_LIO_LIHeptad repeats of MD (namely HR1a and HR1b) are crucial for fusogenic property of Mfn1\nC_LIO_LIMutations disrupting of helical structure of HR1b lead to loss of fusogenic activity of Mfn1\nC_LI