title: Regulation of mitochondrial fusion by the F-box protein Mdm30 involves proteasome-independent turnover of Fzo1.
abstract: Mitochondrial morphology depends on balanced fusion and fission events. A central component of the mitochondrial fusion apparatus is the conserved GTPase Fzo1 in the outer membrane of mitochondria. Mdm30, an F-box protein required for mitochondrial fusion in vegetatively growing cells, affects the cellular Fzo1 concentration in an unknown manner. We demonstrate that mitochondrial fusion requires a tight control of Fzo1 levels, which is ensured by Fzo1 turnover. Mdm30 binds to Fzo1 and, dependent on its F-box, mediates proteolysis of Fzo1. Unexpectedly, degradation occurs along a novel proteolytic pathway not involving ubiquitylation, Skp1-Cdc53-F-box (SCF) E3 ubiquitin ligase complexes, or 26S proteasomes, indicating a novel function of an F-box protein. This contrasts to the ubiquitin- and proteasome-dependent turnover of Fzo1 in alpha-factor-arrested yeast cells. Our results therefore reveal not only a critical role of Fzo1 degradation for mitochondrial fusion in vegetatively growing cells but also the existence of two distinct proteolytic pathways for the turnover of mitochondrial outer membrane proteins.
authors.affiliation: Institute of Genetics and Center for Molecular Medicine, University of Cologne, D-50923 Cologne, Germany.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Escobar-Henriques
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
mesh_terms: D044783:F-Box Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D044783:F-Box Proteins; C481653:Mdm30 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases