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Structural basis of mitochondrial tethering by mitofusin complexes.

Takumi Koshiba·Scott A Detmer·Jens T Kaiser·Hsiuchen Chen·J Michael McCaffery·David C Chan
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Abstract

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.

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Amino Acid SequenceAmino Acid SubstitutionAnimalsCell LineCrystallography, X-RayDimerizationGTP PhosphohydrolasesHumansHybrid CellsHydrophobic and Hydrophilic InteractionsIntracellular MembranesMembrane FusionMiceMitochondriaModels, MolecularMolecular Sequence DataMutationProtein Structure, SecondaryProtein Structure, TertiaryJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Takumi Koshiba, Scott A Detmer, Jens T Kaiser, Hsiuchen Chen, J Michael McCaffery, David C Chan. 2004-08-06. Structural basis of mitochondrial tethering by mitofusin complexes.. https://doi.org/10.1126/science.1099793

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