Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission

Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein, Dnm1, has been localized to sites of mitochondrial division. Using cryo-electron microscopy (cryo-EM), we have determined the three-dimensional structure of Dnm1 in a GTP-bound state. The 3D map reveals a unique helical assembly for Dnm1 when compared with dynamin, a protein involved in vesicle scission during endocytosis. We also show that upon GTP hydrolysis Dnm1 constricts liposomes and subsequently dissociates from the lipid bilayer. The magnitude of Dnm1 constriction is substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Together, our structural studies support a mechanochemical role for Dnm1 during mitochondrial division.