The role of mitochondria for molybdenum cofactor biosynthesis

线粒体在钼辅因子生物合成中的作用

• 批准号: 33197680
• 负责人: Dr. Florian Bittner
• 金额: --
• 依托单位: Julius Kühn-Institut (JKI) - Bundesforschungsinstitut für Kulturpflanzen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/33197680?language=en
• 关键词: role; mitochondria; molybdenum; cofactor; biosynthesis

It is the aim of this project to study the role of mitochondria for molybdenum cofactor (Moco) biosynthesis and molybdenum-enzyme activity. Until recently it was generally believed that Moco-biosynthesis and molybdenum-enzyme formation exclusively proceed in the cytoplasm. Our preliminary work, however, has shown that a crosstalk exists between Mocosynthesis and availability of [Fe-S]-clusters from mitochondria. The ABC-type transporter ATM3 in the inner membrane of mitochondria is known to export [Fe-S] into the cytoplasm. The knock-out of ATM3, however, impairs not only [Fe-S] export but unexpectedly leads to the accummulation of precursorZ (= first intermediate in Moco-biosynthesis) while the amounts of the subsequent cytoplasmic reaction intermediates of Moco-biosynthesis are severely lowered. This might indicate that the first step of Moco-biosynthesis takes place in mitochondria. - In this project we want to unveil whether precursorZ really is generated inside the mitochondria, and if so, whether the enzyme complex that catalyzes the conversion of precursorZ to molybdopterin, MPT-synthase, is associated with the outer membrane of mitochondria. We want to delineate the role played by the ABC-type transporter ATM3 for Moco-biosynthesis. Further we want to clarify the importance of mitochondria for the maturation of molybdenum-enzymes and provide molecular detail on the cross-talk of Mocoand [Fe-S]-biosynthesis. The combination of different approaches will allow us to get a detailed insight into how mitochondria contribute to Moco-biosynthesis and to the formation of molybdenum-enzymes in the cytoplasm.

该项目的目的是研究线粒体在钼辅因子（Moco）生物合成和钼酶活性中的作用。直到最近，人们普遍认为Moco-生物合成和脱氢酶的形成仅在细胞质中进行。然而，我们的初步工作已经表明，从线粒体的[Fe-S]-簇的Mocosynthesis和可用性之间存在串扰。已知线粒体内膜中的ABC型转运蛋白ATM 3将[Fe-S]输出到细胞质中。然而，ATM 3的敲除不仅损害[Fe-S]输出，而且意外地导致MocorZ（= Moco生物合成中的第一中间体）的重新生成，而随后的Moco生物合成的细胞质反应中间体的量严重降低。这可能表明Moco生物合成的第一步发生在线粒体中。- 在这个项目中，我们想揭示是否真的是在线粒体内产生的，如果是这样，是否酶复合物，催化转化的mptosorZ的mptodopterin，MPT合酶，是与线粒体的外膜。我们想描述ABC型转运蛋白ATM 3在Moco生物合成中所起的作用。此外，我们想澄清线粒体的重要性，成熟的辅酶，并提供分子细节的串扰的Moco和[Fe-S]-生物合成。不同方法的组合将使我们能够详细了解线粒体如何促进Moco生物合成和细胞质中的辅酶形成。