Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

A fuzzy mitochondrial fusion apparatus comes into focus

Nature Reviews Molecular Cell Biology volume 4, pages 468–478 (2003)Cite this article

Key Points

  • Homologues of the large fuzzy onions (Fzo) GTPase are required for mitochondrial fusion in flies, budding yeast, mice and humans. The topology of the Fzo protein in the outer mitochondrial membrane is identical in budding yeast and in mammalian cells, which indicates that Fzo's role in mitochondrial fusion has probably remained intact throughout evolution.

  • The mitochondrial fusion apparatus in both mammalian cells and budding yeast is sensitive to high levels of Fzo expression. Yeast cells express a protein that is known as Mdm30, which regulates the steady-state level of Fzo protein.

  • Fzo homologues contain several predicted coiled-coil domains, a GTPase domain and an intermembrane space loop. Mutations in the GTPase domains of Fzo homologues in flies, budding yeast, mice and humans disrupt mitochondrial fusion, which indicates that GTP binding and/or GTP hydrolysis by Fzo proteins are required for mitochondrial fusion. Studies of coiled-coil domains in mammalian cells and of the intermembrane space loop in yeast cells indicate that these domains also have important roles in mitochondrial fusion.

  • Two other molecules — the dynamin-related, intermembrane-space Mgm1 GTPase and the new outer-membrane protein Ugo1 — are clearly required for mitochondrial fusion in yeast. Mgm1 and Ugo1 form a physical complex with Fzo1.

  • Several putative mitochondrial fusion molecules were isolated in a recent genetic screen for mitochondrial morphology mutants and must now be tested in mitochondrial fusion assays. Another recent study uncovered a family of evolutionarily conserved atypical Rho GTPases, which are known as Miro proteins, that affect mitochondrial morphology in human cells.

  • Clearly, Fzo proteins are required for mitochondrial fusion. However, the mechanistic role of these transmembrane GTPases in mitochondrial tethering and lipid mixing remains elusive. We present a model for mitochondrial fusion that builds on conserved mechanistic strategies for viral and SNARE-mediated fusion pathways.

Abstract

Membrane fusion is fundamental to eukaryotic life. Unlike the predominant intracellular fusion machineries that fuse compartments bounded by a single membrane, the mitochondrial fusion machinery must sequentially fuse the outer and inner mitochondrial membranes. These coordinated fusion events rely on a transmembrane GTPase that is known as fuzzy onions or Fzo. Recent studies have revealed that Fzo has an evolutionarily conserved role in mitochondrial fusion, and they take the first strides in determining the molecular nature of such a role.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mitochondrial fusion — a unique case of membrane fusion.
Figure 2: Fzo proteins mediate mitochondrial fusion in diverse organisms.
Figure 3: The Fzo family of high-molecular-mass transmembrane GTPases.

Similar content being viewed by others

References

  1. Bereiter-Hahn, J. & Voth, M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc. Res. Tech. 27, 198–219 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Nunnari, J. et al. Mitochondrial transmission during mating in Saccharomyces cerevisiae is determined by mitochondrial fusion and fission and the intramitochondrial segregation of mitochondrial DNA. Mol. Biol. Cell 8, 1233–1242 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hales, K. G. & Fuller, M. T. Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90, 121–129 (1997). This paper identified the Fzo GTPase as the first mediator of mitochondrial fusion.

    Article  CAS  PubMed  Google Scholar 

  4. Hermann, G. J. et al. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 143, 359–373 (1998). References 4 and 5 show that the budding yeast Fzo1 protein is required for mitochondrial fusion and describe the topology of the Fzo1 protein in the outer mitochondrial membrane.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rapaport, D., Brunner, M., Neupert, W. & Westermann, B. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J. Biol. Chem. 273, 20150–20155 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Sesaki, H. & Jensen, R. E. UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell Biol. 152, 1123–1134 (2001). This paper describes the Ugo1 protein, a new component of the mitochondrial fusion machinery in budding yeast.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sesaki, H., Southard, S. M., Yaffe, M. P. & Jensen, R. E. Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Mol. Biol. Cell 2003 February 6 (DOI: 10.1091/mbc.E02-12-0788).

  8. Wong, E. D. et al. The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion. J. Cell Biol. 160, 303–311 (2003). References 7 and 8 show that the intermembrane-space protein Mgm1 is required for mitochondrial fusion in budding yeast, and that Mgm1 physically associates with the mitochondrial fusion proteins Ugo1 and Fzo1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Otsuga, D. et al. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 143, 333–349 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sesaki, H. & Jensen, R. E. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147, 699–706 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bleazard, W. et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nature Cell Biol. 1, 298–304 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Labrousse, A. M., Zappaterra, M. D., Rube, D. A. & van der Bliek, A. M. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell 4, 815–826 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. Smirnova, E., Griparic, L., Shurland, D. L. & van der Bliek, A. M. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 12, 2245–2256 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cerveny, K. L., McCaffery, J. M. & Jensen, R. E. Division of mitochondria requires a novel DMN1-interacting protein, Net2p. Mol. Biol. Cell 12, 309–321 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fekkes, P., Shepard, K. A. & Yaffe, M. P. Gag3p, an outer membrane protein required for fission of mitochondrial tubules. J. Cell Biol. 151, 333–340 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mozdy, A. D., McCaffery, J. M. & Shaw, J. M. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 151, 367–380 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tieu, Q. & Nunnari, J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J. Cell Biol. 151, 353–366 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Griparic, L. & van der Bliek, A. M. The many shapes of mitochondrial membranes. Traffic 2, 235–244 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Shaw, J. M. & Nunnari, J. Mitochondrial dynamics and division in budding yeast. Trends Cell Biol. 12, 178–184 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yoon, Y. & McNiven, M. A. Mitochondrial division: new partners in membrane pinching. Curr. Biol. 11, R67–R70 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Westermann, B. Merging mitochondria matters: cellular role and molecular machinery of mitochondrial fusion. EMBO Rep. 3, 527–531 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wong, E. D. et al. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J. Cell Biol. 151, 341–352 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Alexander, C. et al. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nature Genet. 26, 211–215 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Delettre, C. et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genet. 26, 207–210 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Olichon, A. et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J. Biol. Chem. 278, 7743–7746 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Berger, K. H. & Yaffe, M. P. Mitochondrial DNA inheritance in Saccharomyces cerevisiae. Trends Microbiol. 8, 508–513 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Okamoto, K., Perlman, P. S. & Butow, R. A. The sorting of mitochondrial DNA and mitochondrial proteins in zygotes: preferential transmission of mitochondrial DNA to the medial bud. J. Cell Biol. 142, 613–623 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ono, T., Isobe, K., Nakada, K. & Hayashi, J. I. Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Nature Genet. 28, 272–275 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Nakada, K. et al. Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nature Med. 7, 934–940 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Skulachev, V. P. Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem. Sci. 26, 23–29 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Fuller, M. T. in The Development of Drosophila (ed. Martinez-Arias, M. B. A.) 71–147 (Cold Spring Harbor Press, New York, 1993).

    Google Scholar 

  32. Chen, Y. A. & Scheller, R. H. SNARE-mediated membrane fusion. Nature Rev. Mol. Cell Biol. 2, 98–106 (2001).

    Article  CAS  Google Scholar 

  33. Hwa, J. J., Hiller, M. A., Fuller, M. T. & Santel, A. Differential expression of the Drosophila mitofusin genes fuzzy onions (fzo) and dmfn. Mech. Dev. 116, 213–216 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Chen, H. et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 160, 189–200 (2003). This paper characterizes mitochondrial phenotypes of mice that are deficient in either Mfn1 or Mfn2, which are the mammalian Fzo homologues.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rojo, M., Legros, F., Chateau, D. & Lombes, A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J. Cell Sci. 115, 1663–1674 (2002). This paper shows that the topology of human Mfn2 in the outer mitochondrial membrane is identical to the topology reported for yeast Fzo1.

    CAS  PubMed  Google Scholar 

  36. Santel, A. & Fuller, M. T. Control of mitochondrial morphology by a human mitofusin. J. Cell Sci. 114, 867–874 (2001). This paper identifies Mfn1 and Mfn2 as probable mediators of mitochondrial fusion.

    CAS  PubMed  Google Scholar 

  37. Nemoto, Y. & De Camilli, P. Recruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein. EMBO J. 18, 2991–3006 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Smirnova, E., Shurland, D. L., Ryazantsev, S. N. & van der Bliek, A. M. A human dynamin-related protein controls the distribution of mitochondria. J. Cell Biol. 143, 351–358 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pitts, K. R., Yoon, Y., Krueger, E. W. & McNiven, M. A. The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. Mol. Biol. Cell 10, 4403–4417 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ishihara, N., Jofuku, A., Eura, Y. & Mihara, K. Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells. Biochem. Biophys. Res. Commun. 301, 891–898 (2003).

    Article  CAS  PubMed  Google Scholar 

  41. Legros, F., Lombes, A., Frachon, P. & Rojo, M. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol. Biol. Cell 13, 4343–4354 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mattenberger, Y., James, D. I. & Martinou, J. C. Fusion of mitochondria in mammalian cells is dependent on the mitochondrial inner membrane potential and independent of microtubules or actin. FEBS Lett. 538, 53–59 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Fritz, S., Weinbach, N. & Westermann, B. Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. Mol. Biol. Cell 2003 February 6 (DOI: 10.1091/mbc.E02-12-0831).

  44. Dimmer, K. S. et al. Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol. Biol. Cell 13, 847–853 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Patton, E. E., Willems, A. R. & Tyers, M. Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis. Trends Genet. 14, 236–243 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Willems, A. R. et al. SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis. Philos. Trans. R. Soc. Lond. B 354, 1533–1550 (1999).

    Article  CAS  Google Scholar 

  47. Uetz, P. et al. A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Fritz, S., Rapaport, D., Klanner, E., Neupert, W. & Westermann, B. Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion. J. Cell Biol. 152, 683–692 (2001). This paper demonstrates that the yeast Fzo1 protein contains a short loop that is exposed to the intermembrane space, which is required for wild-type mitochondrial fusion.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wattenberg, B. & Lithgow, T. Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. Traffic 2, 66–71 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Borgese, N., Gazzoni, I., Barberi, M., Colombo, S. & Pedrazzini, E. Targeting of a tail-anchored protein to endoplasmic reticulum and mitochondrial outer membrane by independent but competing pathways. Mol. Biol. Cell 12, 2482–2496 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Karbowski, M. et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J. Cell Biol. 159, 931–938 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shepard, K. A. & Yaffe, M. P. The yeast dynamin-like protein, Mgm1p, functions on the mitochondrial outer membrane to mediate mitochondrial inheritance. J. Cell Biol. 144, 711–720 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jones, B. A. & Fangman, W. L. Mitochondrial DNA maintenance in yeast requires a protein containing a region related to the GTP-binding domain of dynamin. Genes Dev. 6, 380–389 (1992).

    Article  CAS  PubMed  Google Scholar 

  54. Hinshaw, J. E. Dynamin and its role in membrane fission. Annu. Rev. Cell Dev. Biol. 16, 483–519 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Fukushima, N. H., Brisch, E., Keegan, B. R., Bleazard, W. & Shaw, J. M. The GTPase effector domain sequence of the Dnm1p GTPase regulates self-assembly and controls a rate-limiting step in mitochondrial fission. Mol. Biol. Cell 12, 2756–2766 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pelloquin, L., Belenguer, P., Menon, Y., Gas, N. & Ducommun, B. Fission yeast Msp1 is a mitochondrial dynamin-related protein. J. Cell Sci. 112, 4151–4161 (1999).

    CAS  PubMed  Google Scholar 

  57. Misaka, T., Miyashita, T. & Kubo, Y. Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization, and effect on mitochondrial morphology. J. Biol. Chem. 277, 15834–15842 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Verma, D. P. Cytokinesis and building of the cell plate in plants. Annu. Rev. Plant Physiol. Plant Mol. Biol. 52, 751–784 (2001).

    Article  CAS  PubMed  Google Scholar 

  59. Nelson, D. R., Felix, C. M. & Swanson, J. M. Highly conserved charge-pair networks in the mitochondrial carrier family. J. Mol. Biol. 277, 285–308 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Zimmerberg, J., Vogel, S. S. & Chernomordik, L. V. Mechanisms of membrane fusion. Annu. Rev. Biophys. Biomol. Struct. 22, 433–466 (1993).

    Article  CAS  PubMed  Google Scholar 

  61. Lentz, B. R., Malinin, V., Haque, M. E. & Evans, K. Protein machines and lipid assemblies: current views of cell membrane fusion. Curr. Opin. Struct. Biol. 10, 607–615 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Bullough, P. A., Hughson, F. M., Skehel, J. J. & Wiley, D. C. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37–43 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Sutton, R. B., Fasshauer, D., Jahn, R. & Brunger, A. T. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 å resolution. Nature 395, 347–353 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Ruigrok, R. W. et al. Conformational changes in the hemagglutinin of influenza virus which accompany heat-induced fusion of virus with liposomes. Virology 155, 484–497 (1986).

    Article  CAS  PubMed  Google Scholar 

  65. Carr, C. M., Chaudhry, C. & Kim, P. S. Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc. Natl Acad. Sci. USA 94, 14306–14313 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hanson, P. I., Roth, R., Morisaki, H., Jahn, R. & Heuser, J. E. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 90, 523–535 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Lin, R. C. & Scheller, R. H. Structural organization of the synaptic exocytosis core complex. Neuron 19, 1087–1094 (1997).

    Article  CAS  PubMed  Google Scholar 

  68. Westermann, B. & Neupert, W. Mitochondria-targeted green fluorescent proteins: convenient tools for the study of organelle biogenesis in Saccharomyces cerevisiae. Yeast 16, 1421–1427 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Esser, K., Tursun, B., Ingenhoven, M., Michaelis, G. & Pratje, E. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1. J. Mol. Biol. 323, 835–843 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Klambt, C. EGF receptor signalling: the importance of presentation. Curr. Biol. 10, R388–R391 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Fransson, A., Ruusala, A. & Aspenstrom, P. Atypical rho GTPases have roles in mitochondrial homeostasis and apoptosis. J. Biol. Chem. 278, 6495–6502 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Peters, C. & Mayer, A. Ca2+/calmodulin signals the completion of docking and triggers a late step of vacuole fusion. Nature 396, 575–580 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Wolff, A. M., Petersen, J. G., Nilsson-Tillgren, T. & Din, N. The open reading frame YAL048c affects the secretion of proteinase A in S. cerevisiae. Yeast 15, 427–434 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Skehel, J. J. & Wiley, D. C. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu. Rev. Biochem. 69, 531–569 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Rose, M. D. Nuclear fusion in the yeast Saccharomyces cerevisiae. Annu. Rev. Cell Dev. Biol. 12, 663–695 (1996).

    Article  CAS  PubMed  Google Scholar 

  76. Burke, B. The nuclear envelope: filling in gaps. Nature Cell Biol. 3, E273–E274 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank K. Okamoto for stimulating discussions and comments on the manuscript and M. Mozdy for contributions to figure design. Research in the Shaw laboratory is supported by grants from the National Institutes of Health. A.D.M. was supported in part by an NIH developmental biology training grant.

Author information

Authors and Affiliations

  1. Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, 84112, Utah, USA

    Amy D. Mozdy & Janet M. Shaw

Authors
  1. Amy D. Mozdy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janet M. Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janet M. Shaw.

Related links

Related links

DATABASES

Swiss-Prot

Cdc34

Cdc53

Dnm1

Drp1

Fzo

Fzo1

Mdm30

Mfn1

Mfn2

Mgm1

Miro-1

Miro-2

Skp1

Ugo1

Glossary

FISSION

The division of a mitochondrial tubule into two. Fission events balance fusion events to maintain the wild-type tubular morphology of mitochondria.

MITOCHONDRIAL DNA

Mitochondria contain their own genomes, which encode components of the oxidative phosphorylation machinery and are therefore required for normal mitochondrial function.

DOMINANT OPTIC ATROPHY

The most common form of autosomally inherited optic neuropathy, which is caused by mutations in the OPA1 gene. OPA1 encodes the human homologue of the yeast Mgm1 protein, a dynamin-related GTPase that is implicated in the formation and maintenance of the mitochondrial network.

SNARE PROTEIN

SNARE proteins contain conserved heptad repeats that form coiled-coil structures. SNARE proteins are required for most intracellular membrane fusion events, with the important exception of mitochondrial fusion.

HETEROKARYON

A cell that contains two or more genetically distinct nuclei. Mitochondrial fusion assays in mammalian cells rely on fusing cells with differentially labelled mitochondria and examining whether the mitochondria fuse in the resulting heterokaryons.

DYNAMIN

A GTPase of high molecular mass that mediates the scission of clathrin-coated pits during endocytosis.

F-BOX MOTIF

A protein motif of approximately 50 amino acids that facilitates protein–protein interactions. F-box proteins confer substrate specificity on an invariant core ubiquitylation complex.

SCF COMPLEX

A protein complex formed by Skp1, Cdc53 and a variable F-box protein, which functions as an E3 ubiquitin protein ligase to target proteins for degradation.

COILED-COIL

The coiled-coil motif is an α-helix with a heptad periodicity of amino acids, designated a–g, with hydrophobic amino acids in the a and d positions. These hydrophobic amino acids lie on the same side of the helix and form a face that can interact hydrophobically with another helix to stabilize a protein–protein interaction that is known as a coiled-coil.

HYPOMORPH

A mutant protein that shows only a partial reduction in the activity it influences.

HAEMAGGLUTININ

(HA). The influenza virus envelope glycoprotein that promotes viral infection by mediating the fusion of the viral membrane with the host-cell membrane. Present models for viral entry are based largely on structural and biochemical studies of HA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mozdy, A., Shaw, J. A fuzzy mitochondrial fusion apparatus comes into focus. Nat Rev Mol Cell Biol 4, 468–478 (2003). https://doi.org/10.1038/nrm1125

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1125

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing