Yeast Miro GTPase, Gem1p, Regulates Mitochondrial Morphology via a Novel Pathway

• Published in: The Journal of cell biology 2004-10, Vol.167 (1), p.87-98
• Main Authors: Frederick, Rebecca L., McCaffery, J. Michael, Cunningham, Kyle W., Okamoto, Koji, Shaw, Janet M.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Amino Acid Motifs; Amino Acid Sequence; Apoptosis; Calcium; Cell death; Cell growth; Cells; Cellular biology; Cytoplasm - metabolism; Cytoskeleton - metabolism; DNA, Mitochondrial - metabolism; Enzymes; Glucose - metabolism; Glycerol - metabolism; GTP Phosphohydrolases - metabolism; Image Processing, Computer-Assisted; Intracellular Membranes - metabolism; Mathematical functions; Membrane proteins; Microscopy, Electron, Transmission; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial membranes; Molecular Sequence Data; Multigene Family; Mutation; Pheromones - metabolism; Plasmids - metabolism; Protein Structure, Tertiary; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - physiology; Sequence Homology, Amino Acid; Signal Transduction; Temperature; Yeast; Yeasts
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200405100

Cell signaling events elicit changes in mitochondrial shape and activity. However, few mitochondrial proteins that interact with signaling pathways have been identified. Candidates include the conserved mitochondrial Rho (Miro) family of proteins, which contain two GTPase domains flanking a pair of calcium-binding EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail-anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not an essential component of characterized pathways that regulate mitochondrial dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which are exposed to the cytoplasm, are required for Gem1p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495-6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics.