Limits...
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.

Show MeSH

Related in: MedlinePlus

Domain structure of yeast Miro (Gem1p). (A) Schematic representation of Gem1p domain structure. Indicated are the predicted GTPase I and II domains, EF-hand I and II motifs, and transmembrane segment (TM). (B) Vertical lines indicate substitutions generated in conserved residues of GTPase I and II domains (Table IV). (C) The consensus CaM (Cmd1p)-like EF-hand motif consists of a helix-loop-helix and is indicated (top). Residues important for calcium coordination are bold. Underlined E in Gem1p(EF I) and Gem1p(EF II) were converted to K for mutational analysis (Table IV). (D) Amino acids 633–652 in the Gem1p COOH terminus are predicted to form a membrane spanning α-helix (Wolff et al., 1999). A similar hydrophobic stretch is present in hMiro-1, other Miro homologues (not depicted), and Fis1p, a tail-anchored outer mitochondrial membrane protein. Predicted transmembrane segments are in italics. Positively charged residues predicted to contribute to mitochondrial membrane targeting are indicated in bold.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172521&req=5

fig1: Domain structure of yeast Miro (Gem1p). (A) Schematic representation of Gem1p domain structure. Indicated are the predicted GTPase I and II domains, EF-hand I and II motifs, and transmembrane segment (TM). (B) Vertical lines indicate substitutions generated in conserved residues of GTPase I and II domains (Table IV). (C) The consensus CaM (Cmd1p)-like EF-hand motif consists of a helix-loop-helix and is indicated (top). Residues important for calcium coordination are bold. Underlined E in Gem1p(EF I) and Gem1p(EF II) were converted to K for mutational analysis (Table IV). (D) Amino acids 633–652 in the Gem1p COOH terminus are predicted to form a membrane spanning α-helix (Wolff et al., 1999). A similar hydrophobic stretch is present in hMiro-1, other Miro homologues (not depicted), and Fis1p, a tail-anchored outer mitochondrial membrane protein. Predicted transmembrane segments are in italics. Positively charged residues predicted to contribute to mitochondrial membrane targeting are indicated in bold.

Mentions: The single Miro protein in S. cerevisiae, encoded by YAL048C, shares 30% identity and 48% similarity with the human Miro-1 protein. GEM1 (for GTPase EF-hand protein of mitochondria) encodes a 662–amino acid protein with predicted molecular mass of 75.2 kD (Fig. 1 A). The GTPase I domain contains G1, G2, G4, and G5 motifs characteristic of Ras and Rho-like proteins, but lacks an apparent consensus G3 motif and the Rho-specific sequence insert (Bourne et al., 1991; Wennerberg and Der, 2004). The GTPase II domain is not closely related to Ras, Rho, or other GTPase families, but contains recognizable G1, G2, G4, and G5 motifs (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)

Domain structure of yeast Miro (Gem1p). (A) Schematic representation of Gem1p domain structure. Indicated are the predicted GTPase I and II domains, EF-hand I and II motifs, and transmembrane segment (TM). (B) Vertical lines indicate substitutions generated in conserved residues of GTPase I and II domains (Table IV). (C) The consensus CaM (Cmd1p)-like EF-hand motif consists of a helix-loop-helix and is indicated (top). Residues important for calcium coordination are bold. Underlined E in Gem1p(EF I) and Gem1p(EF II) were converted to K for mutational analysis (Table IV). (D) Amino acids 633–652 in the Gem1p COOH terminus are predicted to form a membrane spanning α-helix (Wolff et al., 1999). A similar hydrophobic stretch is present in hMiro-1, other Miro homologues (not depicted), and Fis1p, a tail-anchored outer mitochondrial membrane protein. Predicted transmembrane segments are in italics. Positively charged residues predicted to contribute to mitochondrial membrane targeting are indicated in bold.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Domain structure of yeast Miro (Gem1p). (A) Schematic representation of Gem1p domain structure. Indicated are the predicted GTPase I and II domains, EF-hand I and II motifs, and transmembrane segment (TM). (B) Vertical lines indicate substitutions generated in conserved residues of GTPase I and II domains (Table IV). (C) The consensus CaM (Cmd1p)-like EF-hand motif consists of a helix-loop-helix and is indicated (top). Residues important for calcium coordination are bold. Underlined E in Gem1p(EF I) and Gem1p(EF II) were converted to K for mutational analysis (Table IV). (D) Amino acids 633–652 in the Gem1p COOH terminus are predicted to form a membrane spanning α-helix (Wolff et al., 1999). A similar hydrophobic stretch is present in hMiro-1, other Miro homologues (not depicted), and Fis1p, a tail-anchored outer mitochondrial membrane protein. Predicted transmembrane segments are in italics. Positively charged residues predicted to contribute to mitochondrial membrane targeting are indicated in bold.
Mentions: The single Miro protein in S. cerevisiae, encoded by YAL048C, shares 30% identity and 48% similarity with the human Miro-1 protein. GEM1 (for GTPase EF-hand protein of mitochondria) encodes a 662–amino acid protein with predicted molecular mass of 75.2 kD (Fig. 1 A). The GTPase I domain contains G1, G2, G4, and G5 motifs characteristic of Ras and Rho-like proteins, but lacks an apparent consensus G3 motif and the Rho-specific sequence insert (Bourne et al., 1991; Wennerberg and Der, 2004). The GTPase II domain is not closely related to Ras, Rho, or other GTPase families, but contains recognizable G1, G2, G4, and G5 motifs (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