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Sequential requirements for the GTPase domain of the mitofusin Fzo1 and the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion.

The ability of cells to respire requires that mitochondria undergo fusion and fission of their outer and inner membranes. The means by which levels of fusion 'machinery' components are regulated and the molecular details of how fusion occurs are largely unknown. In Saccharomyces cerevisiae, a central component of the mitochondrial outer membrane (MOM) fusion machinery is the mitofusin Fzo1, a dynamin-like GTPase. We demonstrate that an early step in fusion, mitochondrial tethering, is dependent on the Fzo1 GTPase domain. Furthermore, the ubiquitin ligase SCF(Mdm30) (a SKP1-cullin-1-F-box complex that contains Mdm30 as the F-box protein), which targets Fzo1 for ubiquitylation and proteasomal degradation, is recruited to Fzo1 as a consequence of a GTPase-domain-dependent alteration in the mitofusin. Moreover, evidence is provided that neither Mdm30 nor proteasome activity are necessary for tethering of mitochondria. However, both Mdm30 and proteasomes are critical for MOM fusion. To better understand the requirement for the ubiquitin-proteasome system in mitochondrial fusion, we used the N-end rule system of degrons and determined that ongoing degradation of Fzo1 is important for mitochondrial morphology and respiration. These findings suggest a sequence of events in early mitochondrial fusion where Fzo1 GTPase-domain-dependent tethering leads to recruitment of SCF(Mdm30) and ubiquitin-mediated degradation of Fzo1, which facilitates mitochondrial fusion.

Pubmed ID: 21502136


  • Cohen MM
  • Amiott EA
  • Day AR
  • Leboucher GP
  • Pryce EN
  • Glickman MH
  • McCaffery JM
  • Shaw JM
  • Weissman AM


Journal of cell science

Publication Data

May 1, 2011

Associated Grants

  • Agency: NCRR NIH HHS, Id: 1 S10 RR023454-01
  • Agency: NICHD NIH HHS, Id: 5 T32 HD07576-22
  • Agency: NIGMS NIH HHS, Id: GM53466
  • Agency: NIGMS NIH HHS, Id: R01 GM053466

Mesh Terms

  • F-Box Proteins
  • GTP Phosphohydrolases
  • Immunoblotting
  • Immunoprecipitation
  • Membrane Fusion
  • Membrane Proteins
  • Mitochondrial Membranes
  • Mitochondrial Proteins
  • Protein Binding
  • SKP Cullin F-Box Protein Ligases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins