Structure, mechanisms, regulation and assembly of ATP synthase

生物的生命依赖于能量的来源。这种能量来自阳光。它通过绿色植物的光合作用收获，并为我们所吃的食物提供高能量成分。我们在体内通过“燃烧”（氧化）高能量成分来获取能量，以一种受控的方式释放细胞能量，以三磷酸腺苷（简称ATP）分子的形式产生生命燃料。这个过程的关键步骤发生在构成我们组织的细胞内的线粒体中。线粒体是生物“发电站”，充满了数以百万计的微小分子涡轮机，ATP合酶，它们像人造涡轮机一样旋转，大量生产细胞燃料，然后输送到我们身体的各个部位，为它们提供能量，使它们发挥作用。我们非常详细地了解了这些分子涡轮机如何工作的许多方面，但还不知道旋转作用是如何产生的。这个项目的一部分是关于提供关键的缺失信息。细菌也有类似的涡轮机，只是在某些方面不同于人类的涡轮机。我们希望更好地理解这些差异，这样我们就可以设计出药物来杀死致病菌，比如导致结核病的致病菌，方法是在不影响人类的情况下停止致病菌的涡轮机。与人体涡轮机相关，但不属于ATP制造机制的一部分，是一个通道，例如在心脏病发作期间，线粒体的内容物以不受控制的方式释放出来，导致细胞死亡。我们想了解这个毛孔是如何工作的，这样我们就可以帮助设计其他药物来控制毛孔。

Biological life depends on a source of energy. That energy comes from sunlight. It is harvested by photosynthesis in green plants, and provides the high energy components in the foods that we eat. We harvest that energy in our bodies by "burning" (oxidising) the high energy components, releasing cellular energy in a controlled way to generate the fuel of life, in the form of the molecule known as adenosine triphosphate (or ATP for short). The key steps in this process take place in the mitochondria inside the cells that make up our tissues. The mitochondria are biological "power stations" full of millions of tiny molecular turbines, the ATP synthases, that rotate rather like man-made turbines churning out the cellular fuel in massive quantities, which is then delivered to all parts of our bodies to provide the energy to make them function. We understand in great detail many aspects of how these molecular turbines work, but as yet not how the rotary action is generated. Part of this project is about providing that crucial missing information. Bacteria have similar turbines that differ is some respects from the human turbines. We want to understand these differences better, so that we can devise drugs to kill pathogenic bacteria, such as the one that causes tuberculosis, by stopping their turbines without influencing the human ones. Associated with the human turbines, but not part of the ATP making machinery, is a channel that becomes opened, for example during a heart attack, letting out the contents of the mitochondria in an uncontrolled way leading to the death of the cell. We want to understand how this pore works, so that we can help design other drugs to control the pore.