Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
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DOI：
10.1083/jcb.143.2.359
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发表时间：
1998-10-19
影响因子：
7.8
通讯作者：
Shaw, J M
中科院分区：
文献类型：
--
作者：
Hermann, G J;Thatcher, J W;Mills, J P;Hales, K G;Fuller, M T;Nunnari, J;Shaw, J M
膜融合是建立线粒体室的形态和细胞分布所必需的。在果蝇中，模糊洋葱（fzo） GTPase的突变阻断了精子发生过程中发育调节的线粒体融合事件。在这里，我们报道了模糊洋葱的酵母同源物Fzo1p在线粒体融合中起直接和保守的作用。条件fzo1突变导致线粒体网断裂，并在酵母交配过程中阻止线粒体融合。Fzo1p是一种线粒体整体膜蛋白，其GTPase结构域暴露于细胞质。改变GTPase结构域中保守残基的点突变不会影响Fzo1p的定位，但会破坏线粒体融合。亚细胞器分离表明，Fzo1p跨越外部，并与内部线粒体膜紧密相关。这种拓扑结构可能需要在融合反应期间协调两个线粒体膜的行为。我们提出，模糊洋葱家族的跨膜gtpase作为分子开关，调节线粒体膜对接和/或融合的关键步骤。
Membrane fusion is required to establish the morphology and cellular distribution of the mitochondrial compartment. In Drosophila, mutations in the fuzzy onions (fzo) GTPase block a developmentally regulated mitochondrial fusion event during spermatogenesis. Here we report that the yeast orthologue of fuzzy onions, Fzo1p, plays a direct and conserved role in mitochondrial fusion. A conditional fzo1 mutation causes the mitochondrial reticulum to fragment and blocks mitochondrial fusion during yeast mating. Fzo1p is a mitochondrial integral membrane protein with its GTPase domain exposed to the cytoplasm. Point mutations that alter conserved residues in the GTPase domain do not affect Fzo1p localization but disrupt mitochondrial fusion. Suborganellar fractionation suggests that Fzo1p spans the outer and is tightly associated with the inner mitochondrial membrane. This topology may be required to coordinate the behavior of the two mitochondrial membranes during the fusion reaction. We propose that the fuzzy onions family of transmembrane GTPases act as molecular switches to regulate a key step in mitochondrial membrane docking and/or fusion.