Domain Interactions within Fzo1 Oligomers Are Essential for Mitochondrial Fusion

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 th...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-06, Vol.281 (24), p.16599-16606
Main Authors: Griffin, Erik E., Chan, David C.
Format: Article
Language:English
Subjects:
Alleles
Cell Membrane - metabolism
Genetic Complementation Test
Genetic Techniques
GTP Phosphohydrolases - chemistry
GTP Phosphohydrolases - metabolism
Membrane Fusion
Membrane Proteins - chemistry
Mitochondria - metabolism
Mitochondrial Proteins
Models, Genetic
Mutation
Protein Structure, Tertiary
Saccharomyces cerevisiae
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M601847200