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Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission

Nature Structural & Molecular Biology volume 18, pages 20–26 (2011)Cite this article

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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.

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Figure 1: Three-dimensional reconstructions of Dnm1 helices.
Figure 2: Analysis of helical packing of Dnm1.
Figure 3: Dnm1-lipid tubes constrict upon addition of GTP.
Figure 4: The diameters of Dnm1-lipid tubes recover after an initial constriction.
Figure 5: A model for mitochondrial fission.

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Acknowledgements

We thank D. Winkler and A. Steven for technical assistance in acquiring tomograms and P. Flicker, J. Hanover, W. Prinz, J. Evans and J. Heymann for critical discussions and reading of the manuscript. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (J.E.H.) and the Nancy Nossal Fellowship of the NIH, NIDDK (J.A.M.). J.N. is supported by NIH grant R01GM062942, and L.L.L. is supported by NIH postdoctoral fellowship 1F32GM078749.

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Author notes

  1. Elena Ingerman

    Present address: Current address: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.,

Authors and Affiliations

  1. Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Jason A Mears, Shunming Fang & Jenny E Hinshaw

  2. Department of Molecular and Cellular Biology, Center for Genetics and Development, University of California, Davis, Davis, California, USA

    Laura L Lackner, Elena Ingerman & Jodi Nunnari

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Contributions

J.A.M. prepared, imaged and processed the cryo-EM data. L.L.L., E.I. and J.N. made the protein. S.F. processed the data. L.L.L. and J.N. critiqued the manuscript. J.A.M. and J.E.H. analyzed the data and wrote the manuscript.

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Correspondence to Jenny E Hinshaw.

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Mears, J., Lackner, L., Fang, S. et al. Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat Struct Mol Biol 18, 20–26 (2011). https://doi.org/10.1038/nsmb.1949

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