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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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Previously characterized mitochondrial morphology proteins are properly localized in gem1Δ cells. Colocalization of mitochondria and GFP-labeled Dnm1p (A), Mdv1p (B), Fis1p (C), and Mmm1p (D) was observed in log phase GEM1 and gem1Δ cells. Bars, 5 μm.
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fig9: Previously characterized mitochondrial morphology proteins are properly localized in gem1Δ cells. Colocalization of mitochondria and GFP-labeled Dnm1p (A), Mdv1p (B), Fis1p (C), and Mmm1p (D) was observed in log phase GEM1 and gem1Δ cells. Bars, 5 μm.

Mentions: Mitochondrial fragmentation in an fzo1 mutant requires active mitochondrial division. To test whether Gem1p is required for mitochondrial division, we asked if gem1Δ could prevent division and fragmentation in an fzo1Δ mutant strain. In both the gem1Δ fzo1Δ test strain and the GEM1 fzo1Δ control strain, mitochondria fragment in the majority of the population (91.1%, 99.0% respectively, Table III). Similar results were obtained when the temperature-sensitive fzo1-1 allele was used for these studies (unpublished data). Moreover, in gem1Δ cells, components of the division machinery, including Dnm1p, Mdv1p, and Fis1p (Otsuga et al., 1998; Bleazard et al., 1999; Fekkes et al., 2000; Mozdy et al., 2000; Tieu and Nunnari, 2000; Cerveny et al., 2001) were properly localized as mitochondrial puncta (Dnm1p, Mdv1p; Fig. 9, A and B) or uniformly on the mitochondrial network (Fis1p; Fig. 9 C), supporting the notion that division is not impaired in this strain. Steady-state levels of Fis1p, Dnm1p, Mdv1p, and Fzo1p in gem1Δ cells were wild type (unpublished data), suggesting that Gem1p does not regulate stability of these mitochondrial morphology proteins.


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)

Previously characterized mitochondrial morphology proteins are properly localized in gem1Δ cells. Colocalization of mitochondria and GFP-labeled Dnm1p (A), Mdv1p (B), Fis1p (C), and Mmm1p (D) was observed in log phase GEM1 and gem1Δ cells. Bars, 5 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172521&req=5

fig9: Previously characterized mitochondrial morphology proteins are properly localized in gem1Δ cells. Colocalization of mitochondria and GFP-labeled Dnm1p (A), Mdv1p (B), Fis1p (C), and Mmm1p (D) was observed in log phase GEM1 and gem1Δ cells. Bars, 5 μm.
Mentions: Mitochondrial fragmentation in an fzo1 mutant requires active mitochondrial division. To test whether Gem1p is required for mitochondrial division, we asked if gem1Δ could prevent division and fragmentation in an fzo1Δ mutant strain. In both the gem1Δ fzo1Δ test strain and the GEM1 fzo1Δ control strain, mitochondria fragment in the majority of the population (91.1%, 99.0% respectively, Table III). Similar results were obtained when the temperature-sensitive fzo1-1 allele was used for these studies (unpublished data). Moreover, in gem1Δ cells, components of the division machinery, including Dnm1p, Mdv1p, and Fis1p (Otsuga et al., 1998; Bleazard et al., 1999; Fekkes et al., 2000; Mozdy et al., 2000; Tieu and Nunnari, 2000; Cerveny et al., 2001) were properly localized as mitochondrial puncta (Dnm1p, Mdv1p; Fig. 9, A and B) or uniformly on the mitochondrial network (Fis1p; Fig. 9 C), supporting the notion that division is not impaired in this strain. Steady-state levels of Fis1p, Dnm1p, Mdv1p, and Fzo1p in gem1Δ cells were wild type (unpublished data), suggesting that Gem1p does not regulate stability of these mitochondrial morphology proteins.

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