Molecular, cellular and organismal functions of the mitochondrial fusion machinery in animal development

线粒体是细胞器，其功能对所有真核生物王国的细胞和有机体生命至关重要。线粒体也是高度动态的细胞器，经常融合和分裂。然而，到目前为止，线粒体动力学的功能相关性还没有得到很好的理解。提出的研究目标是系统地分析线粒体动力学在动物发育过程中的作用。为此，我们正在利用秀丽隐杆线虫，由于其高度可复制的发育，特别适合于动物发育的研究。我们已经开始在单细胞分辨率上分析秀丽隐杆线虫线粒体融合缺陷突变体的发育。初步结果表明，这些突变体在特定细胞系中表现出分化缺陷，例如肌肉细胞谱系（D谱系）。此外，线粒体未折叠蛋白反应（UPRmt）被激活，该反应将线粒体蛋白质折叠环境的变化与核基因的表达结合起来。结合细胞生物学、遗传和分子方法以及基于质谱的蛋白质组学，我们将从机制上研究这两种反应，并确定它们被介导的分子途径。

Mitochondria are cellular organelles whose function is critical for cellular and organismal life throughout all eukaryotic kingdoms. Mitochondria are also highly dynamic organelles that often fuse and divide. However, to date, the functional relevance of mitochondrial dynamics is not well understood. Goal of the proposed studies is to systematically analyze the role of mitochondrial dynamics in the context of animal development. To that end, we are taking advantage of the nematode Caenorhabditis elegans, which due to its highly reproducible development is particularly amenable to studies on animal development. We have begun to analyze the development of C. elegans mutants defective in mitochondrial fusion at single cell resolution. Preliminary results suggest that these mutants exhibit defective differentiation in specific cell lineages, such as a muscle cell lineage (the D lineage). In addition, the mitochondrial unfolded protein response (UPRmt), which couples changes in the protein-folding environment in mitochondria to the expression of nuclear genes, is activated. Using a combination of cell biological, genetic and molecular approaches as well as mass-spectrometry based proteomics, we will study these two responses mechanistically and define the molecular pathways through which they are mediated.