Asymmetric inheritance of mitochondria in yeast

酵母线粒体的不对称遗传

• 批准号: 433461293
• 负责人: Professor Dr. Benedikt Westermann
• 金额: --
• 依托单位: Arbeitsgruppe für Zellbiologie und Elektronenmikroskopie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/433461293?language=en
• 关键词: Asymmetric; inheritance; mitochondria; yeast

During cell division not only the chromosomes in the nucleus, but also all membrane-bounded organelles have to be inherited by transport and partitioning mechanisms. In some cell types – such as stem cells or budding yeasts – asymmetric cell division produces cells with different properties. During stem cell division young and undamaged mitochondria are maintained in the stem cell lineage, whereas in yeast cells young mitochondria are preferentially inherited from the mother to the bud. The molecular mechanisms of asymmetric partitioning of mitochondria and the selection of the "fittest" organelles are largely unknown and will be investigated using baker’s yeast Saccharomyces cerevisiae as a model system. Our previous results show that the myosin motor protein Myo2 transports mitochondria along actin filaments into the bud, while at the same time some mitochondria are anchored by specific protein complexes to the plasma membrane of the mother cell to retain them. The mitochondrial outer membrane protein Alo1 is a novel interaction partner of Myo2, and we are investigating its role in the protection of mitochondria against oxidative damage and the selection of the "fittest" mitochondria for transport into the bud. Ufo1 is a genetic interaction partner of Myo2 and presumably plays an important role as a subunit of an ubiquitin ligase in the regulation of mitochondrial inheritance. Cytosolic protein aggregates which are generated by heat shock or aging are recruited to the mitochondrial surface to retain them in the mother and prevent their inheritance to the daughter cell. Promising preliminary results show that the mitochondrial protein import machinery plays a crucial role in immobilization of these aggregates. The mechanisms of retrograde mitochondrial transport are almost completely unknown and presumably are based on binding of mitochondria to actin cables that grow from the bud neck towards the mother cell. The investigation of these processes promises a detailed understanding of the processes that determine the asymmetric inheritance of mitochondria and consequently cellular aging.

在细胞分裂过程中，不仅细胞核中的染色体，而且所有膜结合的细胞器都必须通过运输和分配机制遗传。在某些细胞类型中，如干细胞或芽殖酵母，不对称细胞分裂产生具有不同特性的细胞。在干细胞分裂期间，年轻且未受损的线粒体维持在干细胞谱系中，而在酵母细胞中，年轻的线粒体优先从母体遗传给芽。线粒体的不对称分配和选择的“最合适的”细胞器的分子机制在很大程度上是未知的，将使用面包酵母酿酒酵母作为模型系统进行研究。我们以前的研究结果表明，肌球蛋白马达蛋白Myo2运输线粒体沿着肌动蛋白丝进入芽，而在同一时间，一些线粒体被锚定的特定蛋白质复合物的母细胞的质膜，以保留它们。线粒体外膜蛋白Alo1是Myo2的一种新的相互作用伙伴，我们正在研究它在保护线粒体免受氧化损伤和选择“最适合”的线粒体运输到芽中的作用。Ufo1是Myo2的遗传相互作用伙伴，并且推测其作为泛素连接酶的亚基在线粒体遗传的调节中起重要作用。由热休克或老化产生的细胞溶质蛋白质聚集体被募集到线粒体表面以将它们保留在母体中并防止它们遗传给子细胞。有希望的初步结果表明，线粒体蛋白质输入机制在这些聚集体的固定化中起着至关重要的作用。线粒体逆行运输的机制几乎完全未知，推测是基于线粒体与从芽颈向母细胞生长的肌动蛋白电缆的结合。对这些过程的研究有望详细了解决定线粒体不对称遗传和细胞衰老的过程。