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© The Rockefeller University Press, 0021-9525/1998//359 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 359-373

Regular Articles

Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p



Greg J. Hermann*, John W. Thatcher*, John P. Mills{ddagger}, Karen G. Hales{ddagger}, Margaret T. Fuller{ddagger}, Jodi Nunnari§, and Janet M. Shaw*

* Department of Biology, University of Utah, Salt Lake City, Utah 84112; {ddagger} Department of Developmental Biology and Department of Genetics, Stanford University School of Medicine, Stanford, California 94305; and § Department of Molecular and Cellular Biology, University of California, Davis, California 95616

Membrane fusion is required to establish the morphology and cellular distribution of the mitochondrial compartment. In Drosophila, mutations in the fuzzy onions (fzo) GTPase block a developmentally regulated mitochondrial fusion event during spermatogenesis. Here we report that the yeast orthologue of fuzzy onions, Fzo1p, plays a direct and conserved role in mitochondrial fusion. A conditional fzo1 mutation causes the mitochondrial reticulum to fragment and blocks mitochondrial fusion during yeast mating. Fzo1p is a mitochondrial integral membrane protein with its GTPase domain exposed to the cytoplasm. Point mutations that alter conserved residues in the GTPase domain do not affect Fzo1p localization but disrupt mitochondrial fusion. Suborganellar fractionation suggests that Fzo1p spans the outer and is tightly associated with the inner mitochondrial membrane. This topology may be required to coordinate the behavior of the two mitochondrial membranes during the fusion reaction. We propose that the fuzzy onions family of transmembrane GTPases act as molecular switches to regulate a key step in mitochondrial membrane docking and/or fusion.

Key Words: GTPase • membrane fusion • mitochondria • mtDNA • organelle morphology

Abbreviations used in this paper: 3-PGK, 3-phosphoglycerate kinase; 5-FOA, 5-fluoro-orotic acid; CoxIV, cytochrome oxidase subunit IV; DAPI, 4',6-diamidino-2-phenylindole; DiOC6, 3,3' dihexyloxacarbocyanine; fzo, fuzzy onions gene; GFP, green fluorescent protein; mtDNA, mitochondrial DNA.

Address all correspondence to Janet M. Shaw, Department of Biology, University of Utah, Salt Lake City, UT 84112. Tel.: (801) 585-6205. Fax: (801) 581-4668. E-mail: shaw{at}bioscience.utah.edu, or Jodi Nunnari, Department of Molecular and Cellular Biology, University of California, Davis, CA 95616. Tel.: (530) 754-9774. Fax: (530) 752-7522. E-mail: fzmito{at}peseta.ucdavis.edu


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