Two Forms Of Opa1 Cooperate To Complete Mitochondria Inner Membrane Fusion

Mitochondrial dynamics, including fusion, fission and migration, are key processes to the proper metabolic function and morphology of the organelle. The key members of mitochondria fusion machinery have been identified to be several dynamin-related protein, however, the working mechanism was largely unclear. Using a in vitro reconstitution platform, we described how mitochondrial inner membrane fusion is accomplished and regulated by two forms of Opa1. We observed that the long, transmembrane form of l-Opa1 is sufficient to mediate membrane tethering, hemifusion and low levels of content release. Addition of processed short form of Opa1 (s-Opa1) helps accelerating fusion an mediates more efficient pore opening. Yet, beyond the equal molar stoichiometry, s-Opa1 inhibits membrane fusion, as seen in conditions of abnormal proteostasis in cells. Based on our results, we propose a gating model for mitochondria inner membrane fusion which emphasize the essence of both long and short form Opa1.