Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae
Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m500807200
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发表时间：
2005-05-13
影响因子：
4.8
通讯作者：
Youle, RJ
中科院分区：
文献类型：
--
作者：
Neutzner, A;Youle, RJ
线粒体形成一个高度动态的网络，由这些细胞器的连续分裂和融合形成。在酵母酿酒酵母中，两种机制参与这一过程，其中之一包括线粒体融合促进GTfzo1。虽然已经提出了F-box蛋白Mdm 30在调节Fzo1稳定性中的作用，但是调节线粒体的分裂与融合比率的分子基础仍然未知。为了辨别线粒体形态的调节机制，我们在细胞周期的不同阶段逮捕细胞，并检查线粒体形态以及线粒体分裂和融合蛋白的稳定性。响应于交配信息素α因子引起的G（1）阻滞，线粒体网络分裂成小块，这伴随着Fzo1的显著下调。交配信息素也引发了组成型启动子的控制下产生的Fzo1的降解，和Fzo1蛋白酶体抑制后稳定，表明Fzo1的降解中的蛋白酶体系统的作用。然而，MDM30的删除交配信息素处理后没有稳定Fzo1，表现出不同的机制，从以前报道的稳态Fzo1调节过程。我们展示了一个例子，在芽殖酵母的生命周期中的线粒体分裂融合比的调节变化。Fzo1在交配信息素的作用下发生蛋白酶体降解，介导了交配过程中线粒体网络的重构。
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 G(1) 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.