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Science 6 August 2004:
Vol. 305. no. 5685, pp. 858 - 862
DOI: 10.1126/science.1099793
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Reports

Structural Basis of Mitochondrial Tethering by Mitofusin Complexes

Takumi Koshiba,1 Scott A. Detmer,1 Jens T. Kaiser,2,3 Hsiuchen Chen,1 J. Michael McCaffery,4 David C. Chan1*

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.

1 Division of Biology, California Institute of Technology, 1200 East California Boulevard, MC114-96, Pasadena, CA 91125, USA.
2 Division of Chemistry, California Institute of Technology, 1200 East California Boulevard, MC114-96, Pasadena, CA 91125, USA.
3 Howard Hughes Medical Institute.
4 Integrated Imaging Center, Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.

* To whom correspondence should be addressed. E-mail: dchan{at}caltech.edu

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