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Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division.

Tieu Q, Nunnari J - J. Cell Biol. (2000)

Bottom Line: Whereas localization of Mdv1p to these structures requires Dnm1p, localization of Mdv1p to mitochondrial membranes does not.Dnm1p-independent targeting of Mdv1p to mitochondria requires MDV2.Our data indicate that MDV2 also functions separately to regulate the assembly of Dnm1p into punctate structures.

View Article: PubMed Central - PubMed

Affiliation: Section of Molecular and Cellular Biology, University of California Davis, Davis, California 95616, USA.

ABSTRACT
Mitochondrial fission is mediated by the dynamin-related GTPase, Dnm1p, which assembles on the mitochondrial outer membrane into punctate structures associated with sites of membrane constriction and fission. We have identified additional nuclear genes required for mitochondrial fission, termed MDV (for mitochondrial division). MDV1 encodes a predicted soluble protein, containing a coiled-coil motif and seven COOH-terminal WD repeats. Genetic and two-hybrid analyses indicate that Mdv1p interacts with Dnm1p to mediate mitochondrial fission. In addition, Mdv1p colocalizes with Dnm1p in fission-mediating punctate structures on the mitochondrial outer membrane. Whereas localization of Mdv1p to these structures requires Dnm1p, localization of Mdv1p to mitochondrial membranes does not. This indicates that Mdv1p possesses a Dnm1p-independent mitochondrial targeting signal. Dnm1p-independent targeting of Mdv1p to mitochondria requires MDV2. Our data indicate that MDV2 also functions separately to regulate the assembly of Dnm1p into punctate structures. In contrast, Mdv1p is not required for the assembly of Dnm1p, but Dnm1p-containing punctate structures lacking Mdv1p are not able to complete division. Our studies suggest that mitochondrial fission is a multi-step process in which Mdv2p regulates the assembly of Dnm1p into punctate structures and together with Mdv1p functions later during fission to facilitate Dnm1p-dependent mitochondrial membrane constriction and/or division.

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Mutations in MDV genes suppress the loss of mtDNA in fzo1-1 cells. Indicated strains were plated onto YPD and YPG and grown at 25 and 37°C.
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Figure 1: Mutations in MDV genes suppress the loss of mtDNA in fzo1-1 cells. Indicated strains were plated onto YPD and YPG and grown at 25 and 37°C.

Mentions: The conditional fzo1-1 mutation abolishes mitochondrial fusion in cells at the nonpermissive temperature of 37°C, causing mitochondrial membranes to fragment rapidly (Hermann et al. 1998). As a secondary consequence of this fragmentation, fzo1-1 cells lose mtDNA and are unable to grow on the nonfermentable carbon source glycerol (Fig. 1; Hermann et al. 1998). We isolated spontaneous suppressor mutants that rescued the fzo1-1 glycerol growth defect at 37°C (Fig. 1 A, see fzo1-1 mdv1-1 and fzo1-1 mdv2-1). These spontaneous suppressor mutations also rescued the glycerol growth defect of a Δfzo1 strain, indicating that they suppress mtDNA loss by bypassing FZO1 function (not shown). Complementation analysis revealed that the fzo1-1 extragenic suppressor mutants represent three groups/genes. Not surprisingly, mutations in one group were allelic to DNM1, which encodes a dynamin-related GTPase required for mitochondrial fission. Previously, we have shown that both mitochondrial fragmentation and mtDNA loss in fzo1-1 cells are suppressed by deleting DNM1 and thus abolishing the opposing mitochondrial fission reaction (Bleazard et al. 1999). The remaining complementation groups represent two novel genes. Like the phenotype of dnm1 cells, mutations in the MDV genes caused almost no growth defects in cells on YPD or YPG media (Fig. 1 A and not shown). Based on our phenotypic analyses, we believe that these genes function in mitochondrial fission.


Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division.

Tieu Q, Nunnari J - J. Cell Biol. (2000)

Mutations in MDV genes suppress the loss of mtDNA in fzo1-1 cells. Indicated strains were plated onto YPD and YPG and grown at 25 and 37°C.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192646&req=5

Figure 1: Mutations in MDV genes suppress the loss of mtDNA in fzo1-1 cells. Indicated strains were plated onto YPD and YPG and grown at 25 and 37°C.
Mentions: The conditional fzo1-1 mutation abolishes mitochondrial fusion in cells at the nonpermissive temperature of 37°C, causing mitochondrial membranes to fragment rapidly (Hermann et al. 1998). As a secondary consequence of this fragmentation, fzo1-1 cells lose mtDNA and are unable to grow on the nonfermentable carbon source glycerol (Fig. 1; Hermann et al. 1998). We isolated spontaneous suppressor mutants that rescued the fzo1-1 glycerol growth defect at 37°C (Fig. 1 A, see fzo1-1 mdv1-1 and fzo1-1 mdv2-1). These spontaneous suppressor mutations also rescued the glycerol growth defect of a Δfzo1 strain, indicating that they suppress mtDNA loss by bypassing FZO1 function (not shown). Complementation analysis revealed that the fzo1-1 extragenic suppressor mutants represent three groups/genes. Not surprisingly, mutations in one group were allelic to DNM1, which encodes a dynamin-related GTPase required for mitochondrial fission. Previously, we have shown that both mitochondrial fragmentation and mtDNA loss in fzo1-1 cells are suppressed by deleting DNM1 and thus abolishing the opposing mitochondrial fission reaction (Bleazard et al. 1999). The remaining complementation groups represent two novel genes. Like the phenotype of dnm1 cells, mutations in the MDV genes caused almost no growth defects in cells on YPD or YPG media (Fig. 1 A and not shown). Based on our phenotypic analyses, we believe that these genes function in mitochondrial fission.

Bottom Line: Whereas localization of Mdv1p to these structures requires Dnm1p, localization of Mdv1p to mitochondrial membranes does not.Dnm1p-independent targeting of Mdv1p to mitochondria requires MDV2.Our data indicate that MDV2 also functions separately to regulate the assembly of Dnm1p into punctate structures.

View Article: PubMed Central - PubMed

Affiliation: Section of Molecular and Cellular Biology, University of California Davis, Davis, California 95616, USA.

ABSTRACT
Mitochondrial fission is mediated by the dynamin-related GTPase, Dnm1p, which assembles on the mitochondrial outer membrane into punctate structures associated with sites of membrane constriction and fission. We have identified additional nuclear genes required for mitochondrial fission, termed MDV (for mitochondrial division). MDV1 encodes a predicted soluble protein, containing a coiled-coil motif and seven COOH-terminal WD repeats. Genetic and two-hybrid analyses indicate that Mdv1p interacts with Dnm1p to mediate mitochondrial fission. In addition, Mdv1p colocalizes with Dnm1p in fission-mediating punctate structures on the mitochondrial outer membrane. Whereas localization of Mdv1p to these structures requires Dnm1p, localization of Mdv1p to mitochondrial membranes does not. This indicates that Mdv1p possesses a Dnm1p-independent mitochondrial targeting signal. Dnm1p-independent targeting of Mdv1p to mitochondria requires MDV2. Our data indicate that MDV2 also functions separately to regulate the assembly of Dnm1p into punctate structures. In contrast, Mdv1p is not required for the assembly of Dnm1p, but Dnm1p-containing punctate structures lacking Mdv1p are not able to complete division. Our studies suggest that mitochondrial fission is a multi-step process in which Mdv2p regulates the assembly of Dnm1p into punctate structures and together with Mdv1p functions later during fission to facilitate Dnm1p-dependent mitochondrial membrane constriction and/or division.

Show MeSH
Related in: MedlinePlus