The function and substrate of the ABC transporters of the mitochondria

在建筑物中，墙分隔房间，门控制入口和出口。以此类推，细胞膜将活细胞的各个部分分隔开来，而转运蛋白则控制着哪些物质可以通过。了解每个转运蛋白的作用是很重要的，因为这将增加我们对膜分离过程的理解，并使我们能够操纵转运。线粒体就像是产生能量的房间，也是许多微妙的化学反应发生的地方（例如制造维生素或金属辅因子）。线粒体膜含有许多转运蛋白，为熔炉提供燃料并为化学反应提供原料。能源、产品和废物需要出口。我们感兴趣的是一种特殊类型的转运蛋白，线粒体的ABC转运蛋白（ATM）。这是因为ATM将重要但尚未识别的物质从线粒体输出到细胞的其他部分，催化关键的生物反应。ABC代表ATP结合盒，这是转运蛋白的一个特征，定义了它所属的组。ATM存在于所有生物体中，缺陷导致人类疾病和植物产量低下。这项研究计划的目的是找出这些线粒体转运蛋白到底转运了什么物质。早期的ATM研究使用酵母，因为这是一种简单的生物体，可以用作实验“模型”。这些研究表明，ATM运输系统的损伤会破坏线粒体外小铁硫结构的产生。这些铁硫结构对于细胞代谢、生长和存活是必不可少的。最近，我们的团队和合作者发现了另一个需要ATM的化学过程，这就是合成氘-有机化合物。这是在植物中发现的，因为酵母没有这种化合物（但人类有）。所以现在我们有两个依赖于ATM的过程，我们可以更好地推测什么可以被传输。其中一种可能性是一种小的硫化合物，它是铁硫结构的一部分，也是钼化合物的一部分。也有可能的是，对于每种金属结构，转运体可以携带非常不同的前体分子。这是一个我们可以相对容易地检验的假设，特别是最近在研究ABC转运蛋白纯制剂方面取得的技术进步。这也使我们能够查看以不同方式损坏的ATM传输器，并找出它们无法正常工作的原因。同样，植物在这方面非常有用，因为发现了几个ATM 3转运蛋白受损的植物品系。最后，我们将了解转运蛋白是如何工作的，它可以运输什么，同时增加我们对依赖于它的细胞过程及其对人类健康和植物生长的重要性的理解。

In buildings, walls separate rooms and doors regulate entry and exit. By analogy, membranes separate parts of living cells, and transporters control which substances move across. Knowing what each transporter does is important, as this will increase our understanding of the processes separated by the membrane, and allow us to manipulate the transport. Mitochondria are like rooms in which energy is generated and where many delicate chemical reactions take place (for instance for making vitamins or metal cofactors). The mitochondrial membranes contain many transporters, to supply the furnaces with fuel and to provide raw materials for chemical reactions. Energy, products and waste then need to be exported. We are interested in a special type of transporter, the ABC transporters of the mitochondria (ATMs). This is because ATMs export vital, but yet unidentified materials out from the mitochondria to the rest of the cell, catalyzing key biological reactions. ABC stands for ATP binding cassette, which is a feature of the transporter protein that defines the group it belongs to. The ATMs are present in all organisms, and defects lead to disease in humans and low yield in plants. The aim of this research proposal is to find out what is exactly the substance transported by these mitochondrial transporters. Earlier studies of ATMs have used yeast, because this is a simple organism to use as an experimental 'model'. These studies revealed that damage to the ATM transport system disrupts the production of small iron-sulphur structures outside the mitochondria. These iron-sulphur structures are essential for cell metabolism, growth and survival. Recently, our group and collaborators have found another chemical process that requires ATM, which is the synthesis of molybdenum-organic compounds. This was discovered in plants, because yeast does not have this compound (but humans do). So now we have two processes that are dependent on ATMs, and we can better speculate what could be transported. One of the possibilities is a small sulphur compound, which is part of the iron-sulphur structures as well as the molybdenum compound. It is also possible that the transporter can carry quite different precursor molecules for each of the metal structures. This is a hypothesis that we can test relatively easily, especially with the technical progress made recently to study pure preparations of ABC transporters. This also allows us to look at the ATM transporters that are damaged in different ways, and find out why they do not work properly. Again, plants have been very useful for this, because several plant lines with a damaged ATM3 transporter were found. In the end, we will learn how the transporter works and what it can transport, while increasing our understanding of the processes in the cell depending on it and their significance for human health and plant growth.