Molecular architecture of a dynamin adaptor: implications for assembly of mitochondrial fission complexes

Abstract

Structural and functional studies of the Mdv1 dimer reveal how this mitochondria-associated adaptor protein orients and stabilizes the assembly of dynamins on membranes to promote mitochondrial fission.

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

“…2, B and C, and supplemental Videos 1-5). In accordance with prior findings, ϳ90% of wild type yeast cells show WT mitochondrial morphology (a continuous, interconnected reticulum with Ͼ2 termini), whereas Ͼ95% of fis1⌬ yeast show defects in mitochondrial fission (netted, collapsed mitochondria or a mitochondrial network with Ͻ3 termini) (32). Expression of Fis1 in fis1⌬ yeast restores WT morphology to ϳ80% of the level observed for wild type yeast.…”

“…7). This model is supported by data herein and previous observations of binary interactions between Fis1-Dnm1 (16), Fis1-Mdv1/NTE domain (18,19,32,33,35), Fis1-Mdv1/WD domain (15), and Mdv1-Dnm1 (11,14,15,(35)(36)(37)44) as well as the aforementioned pull-down data consistent with ternary interactions between all three proteins (16). These interactions are exquisitely balanced for fission machinery assembly (and subsequent fission) as indicated by the sensitivity of Dnm1 distribution to Fis1-E78A expression levels (Fig.…”

“…4 -6). In this model, Fis1-Mdv1 interactions occur through either the NTE (15,16,18,19,32,35) or WD domain (15) with the Fis1-WD interaction too weak to be detected in pull-down experiments. Note that each protein is reported to undergo homotypic interactions (19,32,35,38,65) that are not represented in this model but would aid in building the lattice architecture.…”

“…Briefly, a 2% low melt agarose (Thermo Fisher Scientific) solution containing CSMϩDϪ LTϩ1ϫMET was added to a 3-well depression slide (VWR) and was leveled off by covering with an additional slide. The yeast were imaged for mito-RFP, and the resulting confocal projections were assessed for WT or fission mutant morphology according to published procedures (32).…”

miR-484 regulates mitochondrial network through targeting Fis1

“…such as Fis1, MFF, Mfn 1, Mfn 2, Drp1, Opa1, mitochondrial ubiquitin ligase, mitochondrial protein 18 kDa, Pink 1, Parkin, and so on 50 . These proteins have an important role in a variety of fields, such as neurobiology, heart, cancers and kidney.…”