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Published August 6, 2004 | public
Journal Article

Structural Basis of Mitochondrial Tethering by Mitofusin Complexes

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.

Additional Information

© 2004 American Association for the Advancement of Science. 30 April 2004; accepted 30 June 2004. We are grateful to D. Rees, J. Nunnari, and R. Deshaies for helpful discussions. We thank the staff of the Advanced Light Source at Berkeley Lab. We thank P. Huang for advice on structural analysis. T.K. was supported by a Gosney Foundation postdoctoral fellowship; J.T.K. is an HHMI Research Associate. This work was supported by the National Institute of Health (R01 GM62967). D.C.C. is a Bren Scholar, Rita Allen Scholar, and Beckman Young Investigator. Atomic coordinates and structure factors have been deposited in the Protein Data Bank, accession code 1T3J.

Additional details

Created:
August 19, 2023
Modified:
October 18, 2023