Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae.
Mitochondria form a highly dynamic network that is shaped by continuous fission and fusion of these organelles. In the yeast Saccharomyces cerevisiae two machineries are involved in this process, one of which includes the mitochondrial fusion promoting GTPase Fzo1. Although a role for the F-box protein Mdm30 in regulating the stability of Fzo1 has been proposed, the molecular basis for the regulation of the fission to fusion ratio of mitochondria remains unknown. To discern the mechanism of the regulation of mitochondrial morphology, we arrested cells at different stages of the cell cycle and examined mitochondrial morphology as well as the stability of mitochondrial fission and fusion proteins. In response to a G1 arrest evoked by the mating pheromone alpha factor the mitochondrial network fragmented into small pieces, which was accompanied by dramatic down-regulation of Fzo1. Mating pheromone also triggered the degradation of Fzo1 produced under the control of a constitutive promoter, and Fzo1 was stabilized upon proteasome inhibition, indicating a role for the proteasome system in the degradation of Fzo1. However, deletion of MDM30 did not stabilize Fzo1 after mating pheromone treatment, showing a different mechanism from the previously reported process of steady state Fzo1 regulation. We show an example for a regulated change of the mitochondrial fission to fusion ratio during the life cycle of budding yeast. Proteasomal degradation of Fzo1 in response to the mating pheromone is proposed to mediate the remodeling of the mitochondrial network during the process of mating.
Neutzner
Albert
A
Biochemistry Section, Surgical Neurological Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA.
Youle
Richard J
RJ
D000818:Animals; D002453:Cell Cycle; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila; D044783:F-Box Proteins / Q000737:chemistry; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry; D015739:Nocodazole / Q000494:pharmacology; D010675:Pheromones / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D044783:F-Box Proteins; C481653:Mdm30 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D004247:DNA; D046988:Proteasome Endopeptidase Complex; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; D015739:Nocodazole