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

动物发育中线粒体融合机制的分子、细胞和有机体功能

• 批准号: 327062981
• 负责人: Professorin Dr. Barbara Conradt
• 金额: --
• 依托单位: Division of Biosciences
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/327062981?language=en
• 关键词: Molecular; cellular; organismal; functions; mitochondrial

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.

线粒体是细胞器，其功能对所有真核生物界的细胞和生物体生命至关重要。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很好地理解。拟议研究的目标是系统地分析线粒体动力学在动物发育中的作用。为此，我们正在利用秀丽隐杆线虫，由于其高度可重复的发育，特别适合动物发育研究。我们已经开始分析C. elegans突变体在单细胞分辨率下线粒体融合缺陷。初步结果表明，这些突变体在特定的细胞谱系中表现出有缺陷的分化，例如肌细胞谱系（D谱系）。此外，线粒体未折叠蛋白反应（UPRmt），其将线粒体中蛋白质折叠环境的变化与核基因的表达偶联，被激活。使用细胞生物学，遗传学和分子方法以及基于质谱的蛋白质组学的组合，我们将研究这两种反应的机制，并确定它们介导的分子途径。