Article

Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission

Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nature Structural & Molecular Biology (Impact Factor: 11.63). 01/2011; 18(1):20-6. DOI: 10.1038/nsmb.1949
Source: PubMed

ABSTRACT Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.

0 Followers
 · 
111 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Biological membranes undergo constant remodeling by membrane fission and fusion to change their shape and to exchange material between subcellular compartments. During clathrin-mediated endocytosis, the dynamic assembly and disassembly of protein scaffolds comprising members of the bin-amphiphysin-rvs (BAR) domain protein superfamily constrain the membrane into distinct shapes as the pathway progresses toward fission by the GTPase dynamin. In this Review, we discuss how BAR domain protein assembly and disassembly are controlled in space and time and which structural and biochemical features allow the tight regulation of their shape and function to enable dynamin-mediated membrane fission.
    Cell 02/2014; 156(5):882-892. DOI:10.1016/j.cell.2014.02.017 · 33.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: they fuse and divide. Here we summarize data on the protein machinery driving mitochondrial dynamics in yeast and also discuss the factors that affect the fusion-fission balance. Fission is a general stress response of cells, and in the case of yeast this response appears to be prosurvival. At the same time, even under normal conditions yeast mitochondria undergo continuous cycles of fusion and fission. This seems to be a futile cycle and also expensive from the energy point of view. Why does it exist? Benefits might be the same as in the case of sexual reproduction. Indeed, mixing and separating of mitochondrial content allows mitochondrial DNA to segregate and recombine randomly, leading to high variation in the numbers of mutations per individual mitochondrion. This opens a possibility for effective purifying selection-elimination of mitochondria highly contaminated by deleterious mutations. The beneficial action presumes a mechanism for removal of defective mitochondria. We argue that selective mitochondrial autophagy or asymmetrical distribution of mitochondria during cell division could be at the core of such mechanism.
    Oxidative Medicine and Cellular Longevity 07/2013; 2013:139491. DOI:10.1155/2013/139491 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several mitochondrial outer membrane proteins-Fis1, Mff, MiD49, and MiD51-have been proposed to promote mitochondrial fission by recruiting the GTPase Drp1, but fundamental issues remain concerning their function. A recent study supported such a role for Mff, but not for Fis1. In addition, it is unclear whether MiD49 and MiD51 activate or inhibit fission because their overexpression causes extensive mitochondrial elongation. It is also unknown whether these proteins can act in the absence of one another to mediate fission. Using Fis1-null, Mff-null, and Fis1/Mff-null cells, we show that both Fis1 and Mff have roles in mitochondrial fission. Moreover, immunofluorescence analysis of Drp1 suggests that Fis1 and Mff are important for the number and size of Drp1 puncta on mitochondria. Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission.
    Molecular biology of the cell 01/2013; 24(5). DOI:10.1091/mbc.E12-10-0721 · 5.98 Impact Factor