Role of mitochondrial:plasma membrane contacts in healthy vision

线粒体是细胞内的结构，为包括人类在内的许多生物的生命提供必要的能量。在大多数细胞内，它们是分散的，并与附近与它们接触的一些其他细胞结构（接触点）形成一个网络。由于视网膜和大脑神经元内的光感受器需要大量的能量，线粒体缺陷与许多疾病有关，包括视觉和神经系统疾病。最近发现，光感受器和神经元有专门的线粒体定位，因为它们与邻近细胞的线粒体一起运行，并与包裹细胞的膜（质膜）接触。这还包括一种叫做系链的结构，它将线粒体连接到质膜上，使它们保持在适当的位置。线粒体和系索的这种排列的作用还有待确定。线粒体附着在质膜上，在这些细胞中进化出了一种特殊的作用。为了更好地理解这种作用以及它与线粒体疾病的关系，这个项目的目的是确定是什么控制着这种特殊的线粒体排列，并观察当线粒体在这些细胞内的定位被破坏时会发生什么。为了实现这一目标，我们将提取并识别细胞内位于线粒体和质膜之间的任何物质。通过分析这些样本，我们将能够发现这些系索是由什么组成的，以及与线粒体定位有关的一些成分。我们将通过检查使用冷冻电子断层扫描技术制作的高细节三维图像来研究绳索的结构。最后，我们将研究在光感受器和神经元内线粒体位置发生改变的斑马鱼。将在不同年龄检查视力，以确定它是如何受到影响的，并使用一系列显微镜方法检查眼睛，以确定细胞的健康状况。所有这些实验将为了解系链的组成和结构以及线粒体和质膜之间的连接所起的作用提供重要的见解。这些发现对于了解这些特征如何与线粒体功能和可能的疾病联系起来至关重要，为未来的研究铺平了道路。

Mitochondria are structures within cells that provide energy essential for life of many organisms including humans. Within most cells they are scattered and form a network with some of the other cellular structures nearby that they are in contact with (contact sites). As the light detecting photoreceptors within the retina and brain neurons require large amounts of energy, defects in mitochondrial have been associated with many diseases including visual and neurological disorders. Photoreceptors and neurons have recently been found to have specialised positioning of mitochondria, as they run alongside mitochondria from neighbouring cells and are in contact with the membrane that encases the cell (plasma membrane). This also includes structures called tethers that attach the mitochondria to the plasma membrane to hold them in place. Both the role of this arrangement of the mitochondria and the tethers is yet to be established.The attachment of the mitochondria to the plasma membrane will have evolved to suit a specialised role within these cells. To better understand this role and how it may relate to mitochondrial disease, the aim of this project is to identify what is controlling this specialised mitochondrial arrangement and to see what happens when the positioning of mitochondria is disrupted within these cells. To achieve this, we will extract and identify anything within the cell that is positioned between the mitochondria and the plasma membrane. By analysing these samples, we will be able to find out what these tethers are made up of and some of the components involved in positioning the mitochondria. We will study the structure of the tethers by examining high detailed three-dimensional images made using a technique called cryo-electron tomography. Finally, we will examine zebrafish that have altered positioning of the mitochondria within photoreceptors and neurons. Vision will be checked at different ages to determine how it is affected and using a range of microscopy methods eyes will be examined to determine the health of the cells. All together these experiments will provide important insight into the components and structure of the tethers and the role of this connection between mitochondria and the plasma membrane. These findings will be essential to understand how these features are linked to mitochondria function and possibly disease, paving the way for future studies.