Investigating the molecular mechanism of mitochondrial tethering

项目摘要 我们感兴趣的是线粒体的细胞内分布之间的动态相互作用， 和细胞功能。线粒体不仅对细胞能量产生很重要， 在细胞周期进程、分化、免疫应答、脂质和钙离子代谢中发挥关键作用 稳态和凋亡性细胞死亡。这些不同的角色与 线粒体形状和细胞位置。因此，异常的线粒体 结构与越来越多的疾病有关。线粒体形状 和位置取决于线粒体动力学的整合和调节活动， 运动性和束缚性。一个关键问题是如何协调这些活动， 线粒体的形状和位置发生特定的变化， 需求要开始解决这个问题，了解这些分子基础， 线粒体活动是必不可少的。虽然线粒体拴系起着关键作用， 线粒体在从酵母到神经元的细胞中的位置和功能，它是最不了解的 塑造和定位线粒体的活动。在这项赠款的目的，我们将解决这一问题， 通过利用简易酵母系统的优势和我们在细胞生物学方面的专业知识， 和生物化学的方法来阐明分子基础，机制，和调节两个 在线粒体的分布和遗传中起作用的系链复合物。理解 细胞用来定位线粒体的基本机制将提供对如何定位线粒体的深入了解。 可利用受调节的线粒体束缚来影响线粒体功能， 整体细胞内稳态和健康。

Project Summary We are interested in the dynamic interplay between the intracellular distribution of mitochondria and cellular function. Mitochondria are important not only for cellular energy production but also play critical roles in cell cycle progression, differentiation, immune responses, lipid and calcium homeostasis, and apoptotic cell death. These diverse roles are intimately connected to mitochondrial shape and cellular position. Thus, it is not surprising aberrant mitochondrial architecture has been implicated in an ever-increasing number of diseases. Mitochondrial shape and position depend on the integrated and regulated activities of mitochondrial dynamics, motility, and tethering. A key question is how these activities are coordinated to drive the context-specific changes in the shape and position of mitochondria required to meet cellular needs. To begin to address this question, an understanding of the molecular basis of these mitochondrial activities is essential. While mitochondrial tethering plays a critical role in mitochondrial position and function in cells from yeast to neurons, it is the least understood of the activities that shape and position mitochondria. In the aims of this grant, we will address this deficit by exploiting the strengths of the facile yeast system and our expertise in cell biological and biochemical approaches to elucidate the molecular basis, mechanism, and regulation of two tether complexes that function in the distribution and inheritance of mitochondria. Understanding fundamental mechanisms used by cells to position mitochondria will provide insight into how regulated mitochondrial tethering can be harnessed to influence mitochondrial function and overall cellular homeostasis and fitness.