Dynamin Assembly Strategies and Adaptor Proteins in Mitochondrial Fission

Abstract

Mitochondrial fission is mediated by a dynamin-related GTPase that assembles at constricted sites on the organelle. The mechanism of this GTPase in fission is related to that of classical dynamin, which severs the necks of clathrin-coated pits at the plasma membrane. Although the scale of these membrane remodeling events differs by an order of magnitude, structural studies reveal variations in the assembly properties of classical and mitochondrial dynamins that accommodate these differences. Despite this progress, structural and mechanistic models have not yet incorporated a growing number of adaptor proteins required for the membrane recruitment and function of mitochondrial dynamins. Here we review the structure and assembly properties of the yeast and mammalian mitochondrial dynamins and discuss what is known about the activities of their adaptor proteins.

A Targeted Mutation Identified through pK Measurements Indicates a Postrecruitment Role for Fis1 in Yeast Mitochondrial Fission

“…Glu (7,39,40). In GST pull-down experiments, the Fis1 cytosolic domain tagged with GST (Fis1⌬TM-GST) bound well to yeast-expressed MBP-Mdv1 (Fig.…”

“…Our findings may help resolve discrepancies between the roles of yeast and mammalian Fis1 in fission (7). In sequential models, Mdv1 acts as an obligate adaptor between Fis1 and Dnm1, but no mammalian Mdv1 ortholog has been identified, suggesting that mammalian and yeast fission mechanisms are divergent.…”

“…We infer that the loss of Fis1/Dnm1 co-IP signal results from a loss of interactions with other protein(s) involved in this Fis1/Dnm1 complex. Candidates include Mdv1, which is thought to act as an adaptor between Fis1 and Dnm1 (7,11,33,43), and Caf4, which also binds Dnm1 and Fis1 (11,12), both of which have reduced binding to Fis1-E78A ( Fig. 3 and supplemental Fig.…”

“…A prevalent model for the early steps in yeast mitochondrial fission holds that localizing Dnm1 from the cytoplasm to the passive anchor Fis1 requires the fungus-specific adaptor Mdv1 (7,9,10). Mdv1 then drives Dnm1 assembly into punctate foci on the mitochondrial surface with subsequent GTP hydrolysis and membrane scission.…”

Dynamin-related Protein 1 Oligomerization in Solution Impairs Functional Interactions with Membrane-anchored Mitochondrial Fission Factor

“…The VD has recently been shown to act as a negative regulator of Drp1 self-assembly (14) with an inherent ability to interact with cardiolipin (CL) present in mitochondrial membranes (21,(23)(24)(25). Studies in yeast have shown that the VD is required for interactions with a mitochondrial adaptor protein (26), but the partner protein identified in that study is not conserved in higher eukaryotes, which suggests that the role of the VD may have evolved in higher organisms to accommodate different regulatory interactions in the cytosol and at the surface of mitochondria.…”