Limits...
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.

Show MeSH

Related in: MedlinePlus

Mdv1p contains a novel NH2-terminal domain, a central coiled-coil domain, and a COOH-terminal WD repeat domain. The coiled-coil domain (amino acids 241–303) was identified as described (Lupas et al. 1991). The amino acid regions of the WD repeats are predicted to be the following: WD1 396–427, WD2 439–469, WD3 500–529, WD4 564–592, WD5 604–632, WD6 643–672, WD7 685–713.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2192646&req=5

Figure 4: Mdv1p contains a novel NH2-terminal domain, a central coiled-coil domain, and a COOH-terminal WD repeat domain. The coiled-coil domain (amino acids 241–303) was identified as described (Lupas et al. 1991). The amino acid regions of the WD repeats are predicted to be the following: WD1 396–427, WD2 439–469, WD3 500–529, WD4 564–592, WD5 604–632, WD6 643–672, WD7 685–713.

Mentions: The MDV1 gene encodes a predicted ∼80-kD soluble cytosolic protein containing at least three distinct regions: a novel NH2-terminal region; a middle region predicted to form a coiled-coil structure; and a COOH-terminal region that contains seven WD repeats, predicted to form a circular seven-bladed propeller structure (Fig. 4; Lupas et al. 1991; Wall et al. 1995; Lambright et al. 1996; Sondek et al. 1996; Smith et al. 1999). The presence of the predicted coiled-coil and WD repeat domains indicates that Mdv1p functions in fission by mediating protein–protein interactions. Database searching identified proteins with similarity and identity to the coiled-coil and WD repeat regions of Mdv1p, but failed to identify any convincing Mdv1p structural homologues in higher eucaryotes outside of these regions (Altschul et al. 1997). Given that the mechanism of mitochondrial fission is conserved, it is likely that if no structural homologues exist, functional Mdv1p homologues will be present in other organisms.


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)

Mdv1p contains a novel NH2-terminal domain, a central coiled-coil domain, and a COOH-terminal WD repeat domain. The coiled-coil domain (amino acids 241–303) was identified as described (Lupas et al. 1991). The amino acid regions of the WD repeats are predicted to be the following: WD1 396–427, WD2 439–469, WD3 500–529, WD4 564–592, WD5 604–632, WD6 643–672, WD7 685–713.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Mdv1p contains a novel NH2-terminal domain, a central coiled-coil domain, and a COOH-terminal WD repeat domain. The coiled-coil domain (amino acids 241–303) was identified as described (Lupas et al. 1991). The amino acid regions of the WD repeats are predicted to be the following: WD1 396–427, WD2 439–469, WD3 500–529, WD4 564–592, WD5 604–632, WD6 643–672, WD7 685–713.
Mentions: The MDV1 gene encodes a predicted ∼80-kD soluble cytosolic protein containing at least three distinct regions: a novel NH2-terminal region; a middle region predicted to form a coiled-coil structure; and a COOH-terminal region that contains seven WD repeats, predicted to form a circular seven-bladed propeller structure (Fig. 4; Lupas et al. 1991; Wall et al. 1995; Lambright et al. 1996; Sondek et al. 1996; Smith et al. 1999). The presence of the predicted coiled-coil and WD repeat domains indicates that Mdv1p functions in fission by mediating protein–protein interactions. Database searching identified proteins with similarity and identity to the coiled-coil and WD repeat regions of Mdv1p, but failed to identify any convincing Mdv1p structural homologues in higher eucaryotes outside of these regions (Altschul et al. 1997). Given that the mechanism of mitochondrial fission is conserved, it is likely that if no structural homologues exist, functional Mdv1p homologues will be present in other organisms.

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