Cellular logistics and functional genomics of mitochondrial inheritance in yeast

线粒体是真核细胞的重要细胞器。它们在细胞分裂时的遗传依赖于一种复杂的机制，该机制确保两个子细胞都可靠地接收线粒体。芽殖酵母是研究细胞不对称分裂过程中线粒体遗传的良好模式生物。线粒体由肌球蛋白马达蛋白运输到正在生长的芽中。与此同时，母细胞中的保留机制确保了线粒体网络的一部分被保留。在衰老的过程中，完整的线粒体优先运输到芽中，而陈旧和受损的线粒体在母细胞中积累，直到死亡。拟议项目的主要目标是鉴定在酵母细胞中介导线粒体运输和分割的蛋白质，并调查决定受损线粒体不对称遗传的过程。我们以前的结果表明，肌球蛋白马达蛋白和线粒体-质膜锚在线粒体分裂中起重要作用，母芽颈的间隔蛋白可能对受损线粒体的不对称分裂起重要作用。随着项目的继续，我们希望确定这些过程所需的其他因素，例如肌球蛋白马达蛋白的线粒体受体。此外，我们想要研究决定年轻和老年线粒体不对称划分的过程，例如母芽颈部的隔膜蛋白。我们期望本项目的研究结果将有助于理解高等真核细胞中线粒体的不对称遗传，如哺乳动物干细胞的细胞分裂和分化。

Mitochondria are essential organelles of eukaryotic cells. Their inheritance upon cell division depends on a complex machinery that ensures that both daughter cells reliably receive mitochondria. Budding yeast Saccharomyces cerevisiae is an excellent model organism to study mitochondrial inheritance in asymmetrically dividing cells. Mitochondria are transported by myosin motor proteins into the growing bud. At the same time, retention mechanisms in the mother cell ensure that a portion of the mitochondrial network is retained. During the process of aging intact mitochondria are preferentially transported into the bud, whereas old and damaged mitochondria accumulate in the mother cell until it dies. Major aims of the proposed project are the identification of proteins that mediate transport and partitioning of mitochondria in yeast cells and the investigation of the processes that determine asymmetric inheritance of damaged mitochondria. Our previous results demonstrate that myosin motor proteins and mitochondria-plasma membrane anchors play important roles in mitochondrial partitioning, and that septins at the mother-bud neck presumably are important for asymmetric partitioning of damaged mitochondria. With the continuation of the project we would like to identify additional factors required for these processes, such as mitochondrial receptors for myosin motor proteins. Furthermore, we would like to investigate the processes that determine the asymmetric partitioning of young and aged mitochondria, such as septins at the mother-bud neck. We expect that the results obtained in this project will contribute to the understanding of asymmetric inheritance of mitochondria also in higher eukaryotic cells, such as cell division and differentiation of mammalian stem cells.