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Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion

Griffin, Erik E. and Chan, David C. (2006) Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion. Journal of Biological Chemistry, 281 (24). pp. 16599-16606. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:GRIjbc06

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Abstract

Mitofusins are conserved GTPases essential for the fusion of mitochondria. These mitochondrial outer membrane proteins contain a GTPase domain and two or three regions with hydrophobic heptad repeats, but little is known about how these domains interact to mediate mitochondrial fusion. To address this issue, we have analyzed the yeast mitofusin Fzo1p and find that mutation of any of the three heptad repeat regions (HRN, HR1, and HR2) leads to a null allele. Specific pairs of null alleles show robust complementation, indicating that functional domains need not exist on the same molecule. Biochemical analysis indicates that this complementation is due to Fzo1p oligomerization mediated by multiple domain interactions. Moreover, we find that two non-overlapping protein fragments, one consisting of HRN/GTPase and the other consisting of HR1/HR2, can form a complex that reconstitutes Fzo1p fusion activity. Each of the null alleles disrupts the interaction of these two fragments, suggesting that we have identified a key interaction involving the GTPase domain and heptad repeats essential for fusion.


Item Type:Article
Additional Information:© 2006 the American Society for Biochemistry and Molecular Biology. Received for publication, February 27, 2006, and in revised form, April 12, 2006 Published, JBC Papers in Press, April 19, 2006, DOI 10.1074/jbc.M601847200 We thank Janet Shaw for stimulating discussions on allelic complementation. This work was supported in part by National Institutes of Health Grant GM62967 (to D.C.C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [D.C.C. was a] Beckman Young Investigator and Bren Scholar.
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Funding AgencyGrant Number
NIHGM62967
Subject Keywords:DYNAMIN-RELATED GTPASE; DOMINANT OPTIC ATROPHY; VIRAL MEMBRANE-FUSION; OUTER-MEMBRANE; SACCHAROMYCES-CEREVISIAE; MAMMALIAN HOMOLOGS; COILED COILS; PROTEIN; MGM1P; MECHANISMS
Issue or Number:24
Record Number:CaltechAUTHORS:GRIjbc06
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:GRIjbc06
Alternative URL:http://dx.doi.org/10.1074/jbc.M601847200
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5937
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:09 Nov 2006
Last Modified:02 Oct 2019 23:27

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