Role of MICOS-dependent cristae membrane dynamics within mitochondria (B12)

在许多人类疾病中，脊膜的超微结构是高度可变和强烈改变的。这种膜的重塑已有50多年的历史(浓缩状态与正统状态相比)，并被证明在细胞凋亡过程中也会发生。MICOS(‘线粒体接触部位和冠部组织系统’)复合体是一个大的膜蛋白复合体，确保了适当的冠状体膜结构。通过使用活细胞受激发射耗尽(STED)纳米显微镜，我们可以显示鸡冠膜是高度动态的，并以一种依赖于MICOS的方式在秒的时间尺度上自我重组。在这个项目中，我们的目标是从分子水平上了解哺乳动物细胞中冠状突膜动力学的机制和生理功能。为了实现这些目标，我们将在活的哺乳动物细胞中应用纳米技术，并结合生化和遗传方法。

The ultrastructure of the cristae membrane is highly variable and strongly altered in numerous human dis-orders. Remodelling of this membrane is known for more than 50 years (condensed vs. orthodox state) and was shown to occur also during apoptosis. The MICOS ('Mitochondrial Contact Site and Cristae Organizing System') complex is a large membrane protein complex ensuring proper cristae membrane architecture. By using live-cell stimulated emission depletion (STED) nanoscopy we could show that cristae membranes are highly dynamic and are reorganising themselves at a time scale of seconds in a MICOS-dependent manner. In this project, we aim to get a molecular understanding of the mechanisms and the physiological function of cristae membrane dynamics in mammalian cells. To achieve these aims we will apply nanoscopic techniques in living mammalian cells in combination with biochemical and genetic methods.