title: Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
abstract: 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.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Hermann
authors.forename: J W
authors.initials: JW
authors.lastname: Thatcher
authors.forename: J P
authors.initials: JP
authors.lastname: Mills
authors.forename: K G
authors.initials: KG
authors.lastname: Hales
authors.forename: M T
authors.initials: MT
authors.lastname: Fuller
authors.forename: J
authors.initials: J
authors.lastname: Nunnari
authors.forename: J M
authors.initials: JM
authors.lastname: Shaw
mesh_terms: D003593:Cytoplasm / Q000201:enzymology; D004272:DNA, Mitochondrial / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007425:Intracellular Membranes / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D016296:Mutagenesis / Q000502:physiology; D018272:Porins / Q000032:analysis; D017434:Protein Structure, Tertiary; D012098:Reproduction / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D013347:Subcellular Fractions / Q000201:enzymology; D013696:Temperature
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018272:Porins; D029701:Saccharomyces cerevisiae Proteins; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases