Function and regulation of the mitochondrial membrane fusion machinery

线粒体是真核细胞中令人惊讶的动态细胞器。在许多类型的细胞中，它们不断地沿着细胞骨架轨迹移动，并频繁地融合和分裂。线粒体动力学对细胞的生存或死亡至关重要，因为它在启动细胞程序性死亡途径(细胞凋亡)中起着关键作用，而线粒体融合构成了抵抗细胞衰老的防御机制。线粒体融合和分裂的分子机制在进化过程中高度保守。因此，它可以方便地在简单的模式生物中进行研究，如酵母菌和丝状真菌。在过去的几年里，在酵母中已经确定了介导线粒体融合的核心机制的三个组成部分和两个调节因子。然而，线粒体膜融合的分子机制还知之甚少，考虑到这一过程的复杂性，可能还存在其他未知的因素。这项拟议的项目旨在利用已建立的和新的体内和体外检测方法，对酵母和粗糙脉孢菌线粒体融合机制的已知蛋白质进行功能表征。此外，酵母中新成分的鉴定和功能鉴定将有助于从分子水平上理解线粒体双膜融合的复杂过程。

Mitochondria are amazingly dynamic organelles of eukaryotic cells. In many cell types, they continuously move along cytoskeletal tracks and frequently fuse and divide. Mitochondrial dynamics is critical for cell life or death, because it plays a key role in the initiation of the programmed cell death pathway (apoptosis), and mitochondrial fusion constitutes a defence mechanism against cellular aging. The molecular machinery mediating mitochondrial fusion and fission has been highly conserved during evolution. Thus, it can be conveniently studied in simple model organisms, such as yeasts and filamentous fungi. During the past few years, three components of the core machinery mediating mitochondrial fusion and two regulatory factors have been identified in yeast. However, the molecular mechanisms of mitochondrial membrane fusion are only poorly understood, and given the complexity of this process additional yet unknown factors likely exist. The proposed project is aimed at the functional characterization of the known proteins of the mitochondrial fusion machinery of yeast and Neurospora crassa employing established and novel in vivo and in vitro assays. Furthermore, the identification and functional characterization of novel components in yeast will help to understand the complex process of mitochondrial double membrane fusion at a molecular level.