title: A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro.
abstract: Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins. The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown. By combining an in vitro mitochondrial fusion assay with electron cryo-tomography (cryo-ET), we visualize the junction between attached mitochondria isolated from Saccharomyces cerevisiae and observe complexes that mediate this attachment. We find that cycles of GTP hydrolysis induce progressive formation of a docking ring structure around extended areas of contact. Further GTP hydrolysis triggers local outer membrane fusion at the periphery of the contact region. These findings unravel key features of mitofusin-dependent fusion of outer membranes and constitute an important advance in our understanding of how mitochondria connect and merge.
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Brandt
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, Sorbonne Universités, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Cavellini
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, Sorbonne Universités, Paris, France.
authors.forename: Mickaël M
authors.identifier: 0000-0002-1372-680X
authors.initials: MM
authors.lastname: Cohen
mesh_terms: D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques / Q000379:methods*; D008561:Membrane Fusion; D063154:Mitochondrial Dynamics; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases
keywords: S. cerevisiae; biophysics; cell biology; cryo-EM; dynamin-related-proteins; membrane fusion; mitochondria; mitochondrial dynamics; mitofusin; structural biology