Mechanisms determining morphology and dynamics of the mitochondrial inner membrane

线粒体采用一种特有的超微结构。它们被双层膜包围，内膜折叠成内陷，称为冠状突起。两种线粒体膜的结构还受到反复发生的融合和裂变事件的影响。在这个项目中，我们计划研究决定酵母线粒体内膜动力学和形态的分子机制。已经确定了在这些进程中发挥核心作用的一些组成部分。重要的例子是MICOS复合体、F1FO-ATP合成酶和GTP酶Mgm1。然而，帮助维持线粒体超微结构的所有因素的完整图景仍然缺乏。此外，目前尚不清楚高等真核生物是否也像一些原生生物和藻类那样拥有单独的内膜分裂机制。我们的初步结果表明，在酵母中，内膜可以在没有外膜动力学的情况下被分裂。我们计划采用全基因组遗传筛选和光学和电子显微镜相结合的方法来识别参与这一过程的成分。此外，我们建议使用一种新的高通量电子显微镜屏幕来系统地识别线粒体超微结构维持所需的基因。我们相信，计划中的实验将大大有助于我们理解决定线粒体内膜形态和动力学的机制。

Mitochondria adopt a characteristic ultrastructure. They are surrounded by a double membrane and the inner membrane folds into invaginations that are called cristae. The structure of both mitochondrial membranes is furthermore influenced by recurring fusion and fission events. In this project, we plan to study the molecular mechanisms that determine the dynamics and morphology of the mitochondrial inner membrane in yeast. Some components that play central roles in these processes have already been identified. Important examples are the MICOS complex, the F1FO-ATP synthase, and the GTPase Mgm1. However, a complete picture of all the factors that help to maintain mitochondrial ultrastructure is still missing. Furthermore, it is currently unknown whether also higher eukaryotes possess a separate machinery for the division of the inner membrane, as it is the case in some protists and algae. Our preliminary results indicate that the inner membrane can be divided in the absence of outer membrane dynamics in yeast. We plan to employ a combination of genome-wide genetic screens and light and electron microscopy to identify the components that are involved in this process. Furthermore, we propose to use a novel high throughput electron microscopy screen to systematically identify genes that are required for mitochondrial ultrastructure maintenance. We are confident that the planned experiments will substantially contribute to our understanding of the mechanisms that determine the morphology and dynamics of the mitochondrial inner membrane.