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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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The assembly of Dnm1p into punctate structures does not required MDV1 function. JNY566 (wild-type, pRS315-DNM1-GFP; A and B) and JNY560 (Δ mdv1, pRS315-DNM1-GFP; C and D) cells were grown in YPG to log phase and Dnm1–GFPp was visualized directly by fluorescence confocal microscopy. Bars, 2 μm.
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Figure 9: The assembly of Dnm1p into punctate structures does not required MDV1 function. JNY566 (wild-type, pRS315-DNM1-GFP; A and B) and JNY560 (Δ mdv1, pRS315-DNM1-GFP; C and D) cells were grown in YPG to log phase and Dnm1–GFPp was visualized directly by fluorescence confocal microscopy. Bars, 2 μm.

Mentions: Given that Mdv1p and Dnm1p interact, we tested whether Mdv1p mediates the mitochondrial attachment and/or distribution of Dnm1p by comparing the localization pattern of Dnm1p in wild-type and Δmdv1 cells. As expected, in wild-type cells, Dnm1–GFPp localizes to punctate structures on the mitochondrial membrane (Fig. 9 B; Otsuga et al. 1998; Sesaki and Jensen 1999). Interestingly, in Δmdv1 cells, the pattern of Dnm1–GFPp localization remained punctate. Furthermore, the distribution and apparent size of these Dnm1p-containing structures on the mitochondria were indistinguishable from Dnm1p-containing punctate structures observed in wild-type cells (Fig. 9 compare B and D, 100%, n = 100). Thus, Dnm1p-containing punctate structures with cytologically wild-type characteristics can form in the absence of Mdv1p, but these structures are not able to complete the division of mitochondrial membranes. This observation suggests that Mdv1p is a relatively late recruit to Dnm1p-containing punctate structures, and thus may function during the process of fission to regulate a rate-limiting step such as membrane constriction and/or division via an interaction with another component.


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)

The assembly of Dnm1p into punctate structures does not required MDV1 function. JNY566 (wild-type, pRS315-DNM1-GFP; A and B) and JNY560 (Δ mdv1, pRS315-DNM1-GFP; C and D) cells were grown in YPG to log phase and Dnm1–GFPp was visualized directly by fluorescence confocal microscopy. Bars, 2 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: The assembly of Dnm1p into punctate structures does not required MDV1 function. JNY566 (wild-type, pRS315-DNM1-GFP; A and B) and JNY560 (Δ mdv1, pRS315-DNM1-GFP; C and D) cells were grown in YPG to log phase and Dnm1–GFPp was visualized directly by fluorescence confocal microscopy. Bars, 2 μm.
Mentions: Given that Mdv1p and Dnm1p interact, we tested whether Mdv1p mediates the mitochondrial attachment and/or distribution of Dnm1p by comparing the localization pattern of Dnm1p in wild-type and Δmdv1 cells. As expected, in wild-type cells, Dnm1–GFPp localizes to punctate structures on the mitochondrial membrane (Fig. 9 B; Otsuga et al. 1998; Sesaki and Jensen 1999). Interestingly, in Δmdv1 cells, the pattern of Dnm1–GFPp localization remained punctate. Furthermore, the distribution and apparent size of these Dnm1p-containing structures on the mitochondria were indistinguishable from Dnm1p-containing punctate structures observed in wild-type cells (Fig. 9 compare B and D, 100%, n = 100). Thus, Dnm1p-containing punctate structures with cytologically wild-type characteristics can form in the absence of Mdv1p, but these structures are not able to complete the division of mitochondrial membranes. This observation suggests that Mdv1p is a relatively late recruit to Dnm1p-containing punctate structures, and thus may function during the process of fission to regulate a rate-limiting step such as membrane constriction and/or division via an interaction with another component.

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