MITOCHONDRIAL FUSION IN YEAST REQUIRES THE TRANSMEMBRANE GTPASE FZO1P

Membrane fusion is required to establish the morphology and cellular d istribution of the mitochondrial compartment. In Drosophila, mutations in the fuzzy onions (fzo) GTPase block a developmentally regulated mi tochondrial fusion event during spermatogenesis. Here we report that t he yeast orthologue of fuzzy onions, Fzo1p, plays a direct and conserv ed role in mitochondrial fusion. A conditional fzo1 mutation causes th e mitochondrial reticulum to fragment and blocks mitochondrial fusion during yeast mating. Fzo1p is a mitochondrial integral membrane protei n with its GTPase domain exposed to the cytoplasm. Point mutations tha t alter conserved residues in the GTPase domain do not affect Fzo1p lo calization but disrupt mitochondrial fusion. Suborganellar fractionati on suggests that Fzo1p spans the outer and is tightly associated with the inner mitochondrial membrane. This topology may be required to coo rdinate the behavior of the two mitochondrial membranes during the fus ion reaction. We propose that the fuzzy onions family of transmembrane GTPases act as molecular switches to regulate a key step in mitochond rial membrane docking and/or fusion.