Role of mitochondrial:plasma membrane contacts in healthy vision

线粒体：质膜接触在健康视力中的作用

• 批准号: MR/X020827/1
• 负责人: Thomas Burgoyne
• 金额: $ 198.24万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX020827%2F1
• 关键词: Role; mitochondrial; plasma; membrane; contacts

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.

线粒体是细胞内的结构，为包括人类在内的许多生物体提供生命所必需的能量。在大多数细胞内，它们分散并与它们接触的附近的一些其他细胞结构形成网络（接触部位）。由于视网膜和脑神经元内的光检测光感受器需要大量的能量，线粒体的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具有线粒体的专门定位，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。这也包括被称为系链的结构，系链将线粒体附着在质膜上以将它们固定在适当的位置。线粒体和系链的这种排列方式的作用还有待确定，线粒体与质膜的连接方式已经进化，以适应这些细胞内的特殊作用。为了更好地了解这种作用以及它如何与线粒体疾病相关，该项目的目的是确定是什么控制着这种专门的线粒体排列，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，我们将提取和识别细胞内位于线粒体和质膜之间的任何东西。通过分析这些样本，我们将能够找出这些系绳是由什么组成的，以及参与定位线粒体的一些组件。我们将通过检查使用称为冷冻电子断层扫描技术制作的高细节三维图像来研究系绳的结构。最后，我们将研究改变了光感受器和神经元内线粒体定位的斑马鱼。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。所有这些实验将提供重要的洞察的组成部分和结构的系绳和线粒体和质膜之间的这种连接的作用。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。