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Mitochondrial membrane remodelling regulated by a conserved rhomboid protease

机译:保守的菱形蛋白酶调节线粒体膜重塑

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Rhomboid proteins are intramembrane serine proteases that activate epidermal growth factor receptor (EGFR) signalling in Drosophila(1). Rhomboids are conserved throughout evolution(2-5), and even in eukaryotes their existence in species with no EGFRs implies that they must have additional roles. Here we report that Saccharomyces cerevisiae has two rhomboids, which we have named Rbd1p and Rbd2p. RBD1 deletion results in a respiratory defect; consistent with this, Rbd1p is localized in the inner mitochondrial membrane and mutant cells have disrupted mitochondria. We have identified two substrates of Rbd1p: cytochrome c peroxidase (Ccp1p); and a dynamin-like GTPase (Mgm1p), which is involved in mitochondrial membrane fusion(6-10). Rbd1p mutants are indistinguishable from Mgm1p mutants, indicating that Mgm1p is a key substrate of Rbd1p and explaining the rbd1Delta mitochondrial phenotype. Our data indicate that mitochondrial membrane remodelling is regulated by cleavage of Mgm1p and show that intramembrane proteolysis by rhomboids controls cellular processes other than signalling. In addition, mitochondrial rhomboids are conserved throughout eukaryotes and the mammalian homologue, PARL(11), rescues the yeast mutant, suggesting that these proteins represent a functionally conserved subclass of rhomboid proteases. [References: 30]
机译:菱形蛋白是膜内丝氨酸蛋白酶,可激活果蝇中的表皮生长因子受体(EGFR)信号传导(1)。菱形在整个进化过程中都是保守的(2-5),即使在真核生物中,它们在没有EGFR的物种中的存在也意味着它们必须具有其他作用。在这里,我们报告啤酒酵母有两个菱形,我们将其命名为Rbd1p和Rbd2p。 RBD1缺失导致呼吸系统缺陷;与此相符,Rbd1p位于线粒体内膜,突变细胞破坏了线粒体。我们确定了Rbd1p的两个底物:细胞色素c过氧化物酶(Ccp1p);另一类是与动力蛋白类似的GTPase(Mgm1p),它参与线粒体膜融合(6-10)。 Rbd1p突变体与Mgm1p突变体没有区别,表明Mgm1p是Rbd1p的关键底物,并解释了rbd1Delta线粒体表型。我们的数据表明线粒体膜重塑是由Mgm1p的裂解调节,并表明菱形的膜内蛋白水解控制除信号传导以外的细胞过程。此外,线粒体菱形在整个真核生物中都被保守,哺乳动物同源物PARL(11)拯救了酵母突变体,表明这些蛋白代表了功能上保守的菱形蛋白酶的亚类。 [参考:30]

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