Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway

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 Gem 1 p (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 Gem 1 p 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 Gem 1 p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6,495-6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem I p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics.