title: The novel F-box protein Mfb1p regulates mitochondrial connectivity and exhibits asymmetric localization in yeast.
abstract: Although it is clear that mitochondrial morphogenesis is a complex process involving multiple proteins in eukaryotic cells, little is known about regulatory molecules that modulate mitochondrial network formation. Here, we report the identification of a new yeast mitochondrial morphology gene called MFB1 (YDR219C). MFB1 encodes an F-box protein family member, many of which function in Skp1-Cdc53/Cullin-F-box protein (SCF) ubiquitin ligase complexes. F-box proteins also act in non-SCF complexes whose functions are not well understood. Although cells lacking Mfb1p contain abnormally short mitochondrial tubules, Mfb1p is not essential for known pathways that determine mitochondrial morphology and dynamics. Mfb1p is peripherally associated with the mitochondrial surface. Coimmunoprecipitation assays reveal that Mfb1p interacts with Skp1p in an F-box-dependent manner. However, Mfb1p does not coimmunoprecipitate with Cdc53p. The F-box motif is not essential for Mfb1p-mediated mitochondrial network formation. These observations suggest that Mfb1p acts in a complex lacking Cdc53p required for mitochondrial morphogenesis. During budding, Mfb1p asymmetrically localizes to mother cell mitochondria. By contrast, Skp1p accumulates in the daughter cell cytoplasm. Mfb1p mother cell-specific asymmetry depends on the F-box motif, suggesting that Skp1p down-regulates Mfb1p mitochondrial association in buds. We propose that Mfb1p operates in a novel pathway regulating mitochondrial tubular connectivity.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kondo-Okamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohkuni
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kitagawa
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Janet M
authors.initials: JM
authors.lastname: Shaw
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology
chemical_list: D044783:F-Box Proteins; C514103:Mfb1 protein, S cerevisiae; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D010447:Peptide Hydrolases