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.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|