P09 Structure and mechanisms of membrane protein complexes in mitochondrial membrane organization

在本申请中，我们将与其他联盟成员密切合作，通过采用冷冻单细胞生物或从不同细胞和组织中分离的线粒体的聚焦离子束显微镜的cryoET来扩大和加强我们的cryoEM研究，以调查开放问题。这些问题包括作为质子泵工作并在内膜嵴中进行ATP合成的大型膜蛋白复合物的分布和相互排列，以及它们组装的事件和位点的顺序。我们将继续我们的研究如何老化影响哺乳动物线粒体在分子水平上，特别注意ATP合酶二聚体和呼吸链超复合物。最后，我们将继续在动力蛋白样线粒体GTPases的结构和机制上进行成功的合作，以了解它们如何介导线粒体动力学并保持线粒体嵴的形状。

In the present application, we will expand and intensify our cryoEM studies by adopting cryoET of focused ion-beam lamellae of flash-frozen unicellular organisms or mitochondria isolated from different cells and tissues to investigate open questions, in close collaboration with other consortium members. These questions include the distribution and mutual arrangement of the large membrane protein complexes that work as proton pumps and carry out ATP synthesis in the inner membrane cristae, as well as the sequence of events and sites of their assembly. We will resume our studies of how ageing affects mammalian mitochondria at the molecular level, with special attention to the ATP synthase dimers and respiratory chain supercomplexes. Finally, we will continue our successful collaboration on the structure and mechanisms of the dynamin-like mitochondrial GTPases to find out how they mediate mitochondrial dynamics and maintain the shape of mitochondrial cristae.