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

Frederick RL, McCaffery JM, Cunningham KW, Okamoto K, Shaw JM - J. Cell Biol. (2004)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
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.

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Gem1p is not required for pheromone-induced cell death. Cell death was induced by treating log phase cultures with 20 μM α-factor in the presence/absence of the calcineurin inhibitor FK506 (2 μg/ml). Dead cells were visualized after 10 h by methylene blue staining.
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fig10: Gem1p is not required for pheromone-induced cell death. Cell death was induced by treating log phase cultures with 20 μM α-factor in the presence/absence of the calcineurin inhibitor FK506 (2 μg/ml). Dead cells were visualized after 10 h by methylene blue staining.

Mentions: Overexpression of a putative hyperactive Miro-1 variant in COS-7 cells results in a high rate of spontaneous apoptosis (Fransson et al., 2003). Previous studies in yeast demonstrated that apoptosis-like cell death occurs after prolonged treatments with α-factor, a pheromone that induces mating and calcium signaling pathways that help to prevent cell death (Iida et al., 1990; Cyert et al., 1991; Cyert and Thorner, 1992; Foor et al., 1992; Moser et al., 1996; Withee et al., 1997; Muller et al., 2001; Severin and Hyman, 2002). To test whether Gem1p might perform a similar “pro-death” function in yeast, we measured the degree of cell death in wild-type and gem1 mutant cultures after a 10-h treatment with α-factor in the presence and absence of FK506, an inhibitor of calcineurin in the calcium signaling pathway. The levels of cell death in gem1 cultures were indistinguishable from those of wild-type cultures at all incubation times (Fig. 10 and not depicted). Thus, unlike Miro-1 in mammalian cells, Gem1p had no obvious role in these forms of yeast cell death.


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

Frederick RL, McCaffery JM, Cunningham KW, Okamoto K, Shaw JM - J. Cell Biol. (2004)

Gem1p is not required for pheromone-induced cell death. Cell death was induced by treating log phase cultures with 20 μM α-factor in the presence/absence of the calcineurin inhibitor FK506 (2 μg/ml). Dead cells were visualized after 10 h by methylene blue staining.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172521&req=5

fig10: Gem1p is not required for pheromone-induced cell death. Cell death was induced by treating log phase cultures with 20 μM α-factor in the presence/absence of the calcineurin inhibitor FK506 (2 μg/ml). Dead cells were visualized after 10 h by methylene blue staining.
Mentions: Overexpression of a putative hyperactive Miro-1 variant in COS-7 cells results in a high rate of spontaneous apoptosis (Fransson et al., 2003). Previous studies in yeast demonstrated that apoptosis-like cell death occurs after prolonged treatments with α-factor, a pheromone that induces mating and calcium signaling pathways that help to prevent cell death (Iida et al., 1990; Cyert et al., 1991; Cyert and Thorner, 1992; Foor et al., 1992; Moser et al., 1996; Withee et al., 1997; Muller et al., 2001; Severin and Hyman, 2002). To test whether Gem1p might perform a similar “pro-death” function in yeast, we measured the degree of cell death in wild-type and gem1 mutant cultures after a 10-h treatment with α-factor in the presence and absence of FK506, an inhibitor of calcineurin in the calcium signaling pathway. The levels of cell death in gem1 cultures were indistinguishable from those of wild-type cultures at all incubation times (Fig. 10 and not depicted). Thus, unlike Miro-1 in mammalian cells, Gem1p had no obvious role in these forms of yeast cell death.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus