Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission

Mitochondrial fission is important for organelle transport, inheritance, and turnover, and alterations in fission are seen in neurological disease. In mammals, mitochondrial fission is executed by dynamin-related protein 1 (Drp1), a cytosolic guanosine triphosphatase that polymerizes and constricts...

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Bibliographic Details
Published in:The Journal of cell biology 2014-02, Vol.204 (4), p.477-486
Main Authors: Richter, Viviane, Palmer, Catherine S, Osellame, Laura D, Singh, Abeer P, Elgass, Kirstin, Stroud, David A, Sesaki, Hiromi, Kvansakul, Marc, Ryan, Michael T
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Animals
Blotting, Western
Cells, Cultured
Cellular biology
Crystal structure
Crystallization
Crystallography, X-Ray
Dynamins - physiology
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Fibroblasts - cytology
Fibroblasts - metabolism
Fluorescent Antibody Technique
Guanosine Diphosphate - metabolism
HeLa Cells
Humans
Mice
Mice, Knockout
Mitochondria
Mitochondrial Dynamics - physiology
Mitochondrial Proteins - chemistry
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Peptide Elongation Factors - chemistry
Peptide Elongation Factors - genetics
Peptide Elongation Factors - metabolism
Polymerization
Proteins
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Summary:Mitochondrial fission is important for organelle transport, inheritance, and turnover, and alterations in fission are seen in neurological disease. In mammals, mitochondrial fission is executed by dynamin-related protein 1 (Drp1), a cytosolic guanosine triphosphatase that polymerizes and constricts the organelle. Recruitment of Drp1 to mitochondria involves receptors including Mff, MiD49, and MiD51. MiD49/51 form foci at mitochondrial constriction sites and coassemble with Drp1 to drive fission. Here, we solved the crystal structure of the cytosolic domain of human MiD51, which adopts a nucleotidyltransferase fold. Although MiD51 lacks catalytic residues for transferase activity, it specifically binds guanosine diphosphate and adenosine diphosphate. MiD51 mutants unable to bind nucleotides were still able to recruit Drp1. Disruption of an additional region in MiD51 that is not part of the nucleotidyltransferase fold blocked Drp1 recruitment and assembly of MiD51 into foci. MiD51 foci are also dependent on the presence of Drp1, and after scission they are distributed to daughter organelles, supporting the involvement of MiD51 in the fission apparatus.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201311014