Structural basis of mitochondrial tethering by mitofusin complexes.
Vesicle fusion involves vesicle tethering, docking, and membrane merger. We show that mitofusin, an integral mitochondrial membrane protein, is required on adjacent mitochondria to mediate fusion, which indicates that mitofusin complexes act in trans (that is, between adjacent mitochondria). A heptad repeat region (HR2) mediates mitofusin oligomerization by assembling a dimeric, antiparallel coiled coil. The transmembrane segments are located at opposite ends of the 95 angstrom coiled coil and provide a mechanism for organelle tethering. Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondria to become apposed with a uniform gap. Our results suggest that HR2 functions as a mitochondrial tether before fusion.
Division of Biology, California Institute of Technology, 1200 East California Boulevard, MC114-96, Pasadena, CA 91125, USA.
Takumi
T
Koshiba
Scott A
SA
Detmer
Jens T
JT
Kaiser
Hsiuchen
H
Chen
J Michael
JM
McCaffery
David C
DC
Chan
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000502:physiology / Q000648:ultrastructure; D008561:Membrane Fusion; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse