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A conserved mechanism for mitochondria-dependent dynein anchoring

机译:线粒体依赖的动力蛋白锚定的保守机制

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摘要

Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant Schizosaccharomyces pombe Num1 homologue. In addition to its function in dynein anchoring, we find that S. pombe Num1, also known as Mcp5, interacts with and tethers mitochondria to the plasma membrane in S. pombe and Saccharomyces cerevisiae. Thus, the mitochondria and plasma membrane-binding domains of the Num1 homologues, as well as the membrane features these domains recognize, are conserved. In S. pombe, we find that mitochondria impact the assembly and cellular distribution of Num1 clusters and that Num1 clusters actively engaged in mitochondrial tethering serve as cortical attachment sites for dynein. Thus, mitochondria play a critical and conserved role in the formation and distribution of dynein-anchoring sites at the cell cortex and, as a consequence, impact dynein function. These findings shed light on an ancient mechanism of mitochondria-dependent dynein anchoring that is conserved over more than 450 million years of evolution, raising the intriguing possibility that the role mitochondria play in dynein anchoring and function extends beyond yeast to higher eukaryotes.
机译:线粒体锚的功能超出了简单定位线粒体的范围。在发芽的酵母中,线粒体将线粒体锚蛋白Num1组装成簇,从而将线粒体和动力蛋白锚定到细胞皮层。在这里,我们通过检查进化距离遥远的粟酒裂殖酵母Num1同源物的系链功能,探索线粒体在动力蛋白锚固中的保守作用。除了其在动力蛋白锚固中的功能外,我们还发现粟酒裂殖酵母Num1(也称为Mcp5)与粟酒裂殖酵母和酿酒酵母的质膜相互作用,并将线粒体束缚在其质膜上。因此,Num1同源物的线粒体和质膜结合结构域以及这些结构域识别的膜特征得以保留。在粟酒裂殖酵母中,我们发现线粒体影响Num1簇的组装和细胞分布,而活跃参与线粒体束缚的Num1簇充当动力蛋白的皮质附着位点。因此,线粒体在细胞皮质中的动力蛋白固定位点的形成和分布中起着至关重要的作用,并因此影响动力蛋白的功能。这些发现揭示了线粒体依赖的动力蛋白锚定的古老机制,该机制在超过4.5亿年的进化过程中得到了保留,从而增加了线粒体在动力蛋白锚定和功能中发挥作用的有趣可能性,从酵母延伸到了高等真核生物。

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