权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular mechanism of proton pumping by complex I: A single enzyme study

复合物 I 质子泵浦的分子机制：单酶研究

基本信息

批准号：
BB/P005454/1
负责人：
Stephen Muench
金额：
$ 47.87万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP005454%2F1
关键词：
Molecular mechanism proton pumping complex

项目摘要

Mitochondria are the powerhouses of the cells in our body. Complex I is an enzyme complex that plays a crucial role in this process. It uses the energy obtained from chemical reactions to pump positively charged protons across a 5nm thin membrane. This process is not unlike the charging of a battery. Complex I does not always function under optimal conditions and is known to be source of radical oxygen species, which is believed to have important roles in aging. Furthermore, malfunction of complex I has important consequences for (human) health.We like to know how complex I pumps protons across the membrane. Many studies have already been performed in the past, but the pumping mechanism is still unclear and although hypotheses have been formulised, none of these have been experimentally proven. All studies in the past have looked at large ensembles of complex I and form a picture of how these complexes function on average. However, we think that a better understanding of the pumping mechanism can be obtained if we look at these complexes one by one. We have recently developed new experimental methods that are so sensitive they can detect proton pumping by single complexes. In this proposal we want to apply these experiments to study complex I. The results will give us a better understanding on how these complexes function in our mitochondria and what happens when they do not work optimally. The questions we aim to address are of fundamental, 'blue-sky' nature, but on the long term we hope that deeper understanding of the processes that generate energy in our body will help us to tackle diseases often related with aging, including Alzheimer's disease and cancer.

线粒体是我们体内细胞的能量发电站。复合体I是一种酶复合体，在这个过程中起着至关重要的作用。它利用从化学反应中获得的能量将带正电的质子泵送到5纳米的薄膜上。这个过程和给电池充电没什么不同。复合物I并不总是在最佳条件下发挥作用，并且已知是自由基氧的来源，而自由基氧被认为在衰老中起重要作用。此外，复合物I的功能障碍对（人类）健康有重要影响。我们想知道复合体I是如何泵送质子穿过膜的。过去已经进行了许多研究，但泵送机制仍然不清楚，尽管已经提出了假设，但这些都没有得到实验证明。过去的所有研究都着眼于复合体I的大集合，并形成了这些复合体如何平均起作用的图像。然而，我们认为，如果我们逐个观察这些复合物，可以更好地了解泵送机制。我们最近开发了新的实验方法，它们非常灵敏，可以检测到单个配合物的质子泵送。在这个提议中，我们希望将这些实验应用于研究复合体i。结果将使我们更好地了解这些复合体在我们的线粒体中是如何起作用的，以及当它们不起作用时会发生什么。我们的目标是解决基本的、“蓝天”性质的问题，但从长远来看，我们希望对身体产生能量的过程有更深入的了解，这将有助于我们解决通常与衰老有关的疾病，包括阿尔茨海默病和癌症。