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Published online 16 October 2000. doi:10.1083/jcb.151.2.353
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© The Rockefeller University Press, 0021-9525/2000//353 $5.00
The Journal of Cell Biology, Volume 151, Number 2, , 2000 353-366


Original Article

Mdv1p Is a Wd Repeat Protein That Interacts with the Dynamin-Related Gtpase, Dnm1p, to Trigger Mitochondrial Division



Quinton Tieua and Jodi Nunnaria

a Section of Molecular and Cellular Biology, University of California Davis, Davis, California 95616
Section of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616.530-752-7522530-754-9774

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.

Key Words: fission • membrane remodeling • morphology • outer membrane • organelle



© 2000 The Rockefeller University Press

Abbreviations used in this paper: AD, activation domain; BD, binding domain; MBP, maltose-binding protein; ORF, open reading frame.



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