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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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Inner membrane cristae are present in globular gem1Δ mitochondria. Mitochondria in wild-type cells (JSY7000) are tubular in longitudinal sections (A) and spherical in cross section (B) and contain inner membrane cristae. Profiles of globular mitochondria in gem1Δ strains (JSY7002, C–F), are larger than wild type but contain well-developed cristae. n, nucleus. Bars, 1 μm.
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fig4: Inner membrane cristae are present in globular gem1Δ mitochondria. Mitochondria in wild-type cells (JSY7000) are tubular in longitudinal sections (A) and spherical in cross section (B) and contain inner membrane cristae. Profiles of globular mitochondria in gem1Δ strains (JSY7002, C–F), are larger than wild type but contain well-developed cristae. n, nucleus. Bars, 1 μm.

Mentions: To determine whether inner mitochondrial membrane ultrastructure was disrupted in gem1Δ cells, we performed transmission electron microscopy (TEM). Both wild-type and gem1Δ sections contained mitochondrial profiles with well-developed inner membrane cristae (Fig. 4). In wild-type cells, mitochondria in longitudinal sections appeared tubular (Fig. 4 A) and in cross section (Fig. 4 B) were surrounded by a double membrane. gem1Δ sections often exhibited large mitochondrial profiles with double membranes and lighter matrix staining, consistent with the idea that these organelles are swollen (Fig. 4, C–F). These findings provide additional evidence that globular mitochondria in gem1Δ cells are not composed of aggregated tubules. Interestingly, gem1Δ mitochondria in a few TEM sections appeared partially or completely engulfed by vacuoles, suggesting that aberrant mitochondria are turned over via autophagy (unpublished data).


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)

Inner membrane cristae are present in globular gem1Δ mitochondria. Mitochondria in wild-type cells (JSY7000) are tubular in longitudinal sections (A) and spherical in cross section (B) and contain inner membrane cristae. Profiles of globular mitochondria in gem1Δ strains (JSY7002, C–F), are larger than wild type but contain well-developed cristae. n, nucleus. Bars, 1 μm.
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Related In: Results  -  Collection

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fig4: Inner membrane cristae are present in globular gem1Δ mitochondria. Mitochondria in wild-type cells (JSY7000) are tubular in longitudinal sections (A) and spherical in cross section (B) and contain inner membrane cristae. Profiles of globular mitochondria in gem1Δ strains (JSY7002, C–F), are larger than wild type but contain well-developed cristae. n, nucleus. Bars, 1 μm.
Mentions: To determine whether inner mitochondrial membrane ultrastructure was disrupted in gem1Δ cells, we performed transmission electron microscopy (TEM). Both wild-type and gem1Δ sections contained mitochondrial profiles with well-developed inner membrane cristae (Fig. 4). In wild-type cells, mitochondria in longitudinal sections appeared tubular (Fig. 4 A) and in cross section (Fig. 4 B) were surrounded by a double membrane. gem1Δ sections often exhibited large mitochondrial profiles with double membranes and lighter matrix staining, consistent with the idea that these organelles are swollen (Fig. 4, C–F). These findings provide additional evidence that globular mitochondria in gem1Δ cells are not composed of aggregated tubules. Interestingly, gem1Δ mitochondria in a few TEM sections appeared partially or completely engulfed by vacuoles, suggesting that aberrant mitochondria are turned over via autophagy (unpublished data).

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