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J. Cell Biol.,
Volume 143, Number 2, October 19, 1998 359-373
* Department of Biology, University of Utah, Salt Lake City, Utah 84112; 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.
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
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