Monitoring Editor: Gero Steinberg The division of mitochondrial membranes is a complex process mediated by a dynamin-related protein, Dnm1 in yeast, acting in concert with several cofactors. We have identified Mdm36 as a mitochondria-associated protein required for efficient mitochondrial division. Deltamdm36 mutants contain highly interconnected mitochondrial networks that strikingly resemble known fission mutants. Furthermore, mitochondrial fission induced by depolymerization of the actin cytoskeleton is blocked in Deltamdm36 mutants, and the number of Dnm1 clusters on mitochondrial tips is reduced. Double mutant analyses indicate that Mdm36 acts antagonistically to fusion-promoting components, such as Fzo1 and Mdm30. The cell cortex-associated protein Num1 was previously shown to interact with Dnm1 and promote mitochondrial fission. We observed that mitochondria are highly motile and that their localization is not restricted to the cell periphery in Deltamdm36 and Deltanum1 mutants. Intriguingly, colocalization of Num1 and Dnm1 is abolished in the absence of Mdm36. These data suggest that Mdm36 is required for mitochondrial division by facilitating the formation of protein complexes containing Dnm1 and Num1 at the cell cortex. We propose a model that Mdm36-dependent formation of cell cortex anchors is required for the generation of tension on mitochondrial membranes to promote mitochondrial fission by Dnm1.
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