Cryo-EM structures reveal a conformational change of SOPA1 during mitochondrial inner membrane fusion

Mammalian mitochondrial inner membrane fusion is mediated by OPA1(optic atrophy 1). Under physiological condition, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (L-OPA1) and a soluble short isoform (S-OPA1). A combination of L-OPA1 and S-OPA1 are required for membrane fusion, however, the relevant mechanism is not well understood. In this study, we investigate the cryo-EM structures of S-OPA1 coated liposome at nucleotide-free and GTPγS bound states. S-OPA1 exhibits a general structure of dynamin family. It can assemble onto membrane in a helical array with a building block of dimer and thus induce membrane tubulation. A predicted amphipathic helix is discovered to mediate the tubulation activity of S-OPA1. The binding of GTPγS triggers a conformational rotation between GTPase domain and stalk region, resulting the rearrangement of helical lattice and tube expansion. This observation is opposite to the behavior of other dynamin proteins, suggesting a unique role of S-OPA1 in the fusion of mitochondrial inner membrane.