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Reference: Neutzner A and Youle RJ (2005) Instability of the Mitofusin Fzo1 Regulates Mitochondrial Morphology during the Mating Response of the Yeast Saccharomyces cerevisiae. J Biol Chem 280(19):18598-603

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Abstract


Mitochondria form a highly dynamic network, which 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 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 that was accompanied by dramatic downregulation of Fzo1. Mating pheromone also triggered the degradation of Fzo1 produced under the control of a constitutive promotor 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 the first 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.

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Journal Article
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Neutzner A, Youle RJ
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