UGO1 encodes an outer membrane protein required for mitochondrial fusion

Membrane fusion plays an important role in controlling the shape, number, and distribution of mitochondria. In the yeast Saccharomyces cerevisiae, the outer membrane protein Fzolp has been shown to mediate mitochondrial fusion. Using a novel genetic screen, we have isolated new mutants defective in the fusion of their mitochondria. One of these mutants, ugol, shows several similarities to fzol mutants, ugol cells contain numerous mitochondrial fragments instead of the few long, tubular organelles seen in wild-type cells, ugol mutants lose mitochondrial DNA (mtDNA). In zygotes formed by mating two ugol cells, mitochondria do not fuse and mix their matrix contents. Fragmentation of mitochondria and loss of mtDNA in ugol mutants are rescued by disrupting DNM1, a gene required for mitochondrial division. We find that UGO1 encodes a 58-kD protein located in the mitochondrial outer membrane. Ugolp appears to contain a single transmembrane segment, with its NH2 terminus facing the cytosol and its COOH terminus in the intermembrane space. Our results suggest that Ugolp is a new outer membrane component of the mitochondrial fusion machinery.