Abstract
Mitochondria undergo continuous cycles of homotypic fusion and fission, which play an important role in controlling organelle morphology, copy number, and mitochondrial DNA maintenance. Because mitochondria cannot be generated de novo, the motility and distribution of these organelles are essential for their inheritance by daughter cells during division. Mitochondrial Rho (Miro) GTPases are outer mitochondrial membrane proteins with two GTPase domains and two EF-hand motifs, which act as receptors to regulate mitochondrial motility and inheritance. Here we report that although all of these domains are biochemically active, only the GTPase domains are required for the mitochondrial inheritance function of Gem1p (the yeast Miro ortholog). Mutations in either of the Gem1p GTPase domains completely abrogated mitochondrial inheritance, although the mutant proteins retained half the GTPase activity of the wild-type protein. Although mitochondrial inheritance was not dependent upon Ca2+ binding by the two EF-hands of Gem1p, a functional N-terminal EF-hand I motif was critical for stable expression of Gem1p in vivo. Our results suggest that basic features of Miro protein function are conserved from yeast to humans, despite differences in the cellular machinery mediating mitochondrial distribution in these organisms.
| Original language | English |
|---|---|
| Pages (from-to) | 354-362 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 7 2011 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Structure-function analysis of the yeast mitochondrial Rho GTPase, Gem1p : Implications for mitochondrial inheritance. / Koshiba, Takumi; Holman, Holly A.; Kubara, Kenji; Yasukawa, Kai; Kawabata, Shun Ichiro; Okamoto, Koji; Macfarlane, Jane; Shaw, Janet M.
In: Journal of Biological Chemistry, Vol. 286, No. 1, 07.01.2011, p. 354-362.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structure-function analysis of the yeast mitochondrial Rho GTPase, Gem1p
T2 - Implications for mitochondrial inheritance
AU - Koshiba, Takumi
AU - Holman, Holly A.
AU - Kubara, Kenji
AU - Yasukawa, Kai
AU - Kawabata, Shun Ichiro
AU - Okamoto, Koji
AU - Macfarlane, Jane
AU - Shaw, Janet M.
PY - 2011/1/7
Y1 - 2011/1/7
N2 - Mitochondria undergo continuous cycles of homotypic fusion and fission, which play an important role in controlling organelle morphology, copy number, and mitochondrial DNA maintenance. Because mitochondria cannot be generated de novo, the motility and distribution of these organelles are essential for their inheritance by daughter cells during division. Mitochondrial Rho (Miro) GTPases are outer mitochondrial membrane proteins with two GTPase domains and two EF-hand motifs, which act as receptors to regulate mitochondrial motility and inheritance. Here we report that although all of these domains are biochemically active, only the GTPase domains are required for the mitochondrial inheritance function of Gem1p (the yeast Miro ortholog). Mutations in either of the Gem1p GTPase domains completely abrogated mitochondrial inheritance, although the mutant proteins retained half the GTPase activity of the wild-type protein. Although mitochondrial inheritance was not dependent upon Ca2+ binding by the two EF-hands of Gem1p, a functional N-terminal EF-hand I motif was critical for stable expression of Gem1p in vivo. Our results suggest that basic features of Miro protein function are conserved from yeast to humans, despite differences in the cellular machinery mediating mitochondrial distribution in these organisms.
AB - Mitochondria undergo continuous cycles of homotypic fusion and fission, which play an important role in controlling organelle morphology, copy number, and mitochondrial DNA maintenance. Because mitochondria cannot be generated de novo, the motility and distribution of these organelles are essential for their inheritance by daughter cells during division. Mitochondrial Rho (Miro) GTPases are outer mitochondrial membrane proteins with two GTPase domains and two EF-hand motifs, which act as receptors to regulate mitochondrial motility and inheritance. Here we report that although all of these domains are biochemically active, only the GTPase domains are required for the mitochondrial inheritance function of Gem1p (the yeast Miro ortholog). Mutations in either of the Gem1p GTPase domains completely abrogated mitochondrial inheritance, although the mutant proteins retained half the GTPase activity of the wild-type protein. Although mitochondrial inheritance was not dependent upon Ca2+ binding by the two EF-hands of Gem1p, a functional N-terminal EF-hand I motif was critical for stable expression of Gem1p in vivo. Our results suggest that basic features of Miro protein function are conserved from yeast to humans, despite differences in the cellular machinery mediating mitochondrial distribution in these organisms.
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UR - http://www.scopus.com/inward/citedby.url?scp=78650935783&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110.180034
DO - 10.1074/jbc.M110.180034
M3 - Article
C2 - 21036903
AN - SCOPUS:78650935783
VL - 286
SP - 354
EP - 362
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 1
ER -