Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast.
Mitochondrial fusion and fission play important roles for mitochondrial morphology and function. We identified Mdm30 as a novel component required for maintenance of fusion-competent mitochondria in yeast. The Mdm30 sequence contains an F-box motif that is commonly found in subunits of Skp1-Cdc53-F-box protein ubiquitin ligases. A fraction of Mdm30 is associated with mitochondria. Cells lacking Mdm30 contain highly aggregated or fragmented mitochondria instead of the branched tubular network seen in wild-type cells. Deltamdm30 cells lose mitochondrial DNA at elevated temperature and fail to fuse mitochondria in zygotes at all temperatures. These defects are rescued by deletion of DNM1, a gene encoding a component of the mitochondrial division machinery. The protein level of Fzo1, a key component of the mitochondrial fusion machinery, is regulated by Mdm30. Elevated Fzo1 levels in cells lacking Mdm30 or in cells overexpressing Fzo1 from a heterologous promoter induce mitochondrial aggregation in a similar manner. Our results suggest that Mdm30 controls mitochondrial shape by regulating the steady-state level of Fzo1 and point to a connection of the ubiquitin/26S proteasome system and mitochondria.
Fritz
Stefan
S
Institut für Physiologische Chemie, Universität München, Germany.
Weinbach
Nadja
N
Westermann
Benedikt
B
D044783:F-Box Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism*
D044783:F-Box Proteins; C481653:Mdm30 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae