For more than fifty years mitochondria have been known to be the site of cellular respiration by harboring the TCA cycle and the process of oxidative phosphorylation. Recently, other important roles of mitochondria have emerged, which are the regulation of Programmed Cell Death and the biosynthesis of iron-sulfur (Fe/S) clusters. The latter pathway is being unraveled rapidly in the model organism Saccharomyces cerevisiae (Baker's yeast), paving the way to the characterization of homo-logous gene products in humans and plants. The biosynthesis of Fe/S clusters appears to be an essential function of yeast mitochondria because they supply the Fe/S clusters for a number of cytosolic Fe/S proteins. Although a yeast mitochondrial transporter and an intermembrane-space protein thought to be involved in the export of Fe/S clusters have been identified, little is known about the process of transport and the fate of the clusters after export from the organelle. Therefore, the objective of this research proposal is to study the cytosolic pathway of Fe/S protein assembly in yeast. First, a genetic strategy will be designed in order to identify novel genes involved. Second, a biochemical assay will be developed to study the export mechanism in vitro and to characterize the specific roles of the identified gene products. The applicant has several years of research experience in plant mitochondria, and the proposed research will therefore broaden her expertise in mitochondrial metabolism. In addition, it will provide her with new skills including working with the model organism yeast and molecular genetic techniques Through the very nature of the research topic (Fe/S clusters which are generally involved in electron transfer) the applicant will extend her knowledge into the physical aspects of this field of biochemistry. In the future, the acquired expertise could be used to set up a research group investigating the almost unexplored field of Fe/S protein biogenesis in plants, including their vital role in respiration and photo-synthesis. With her expertise, the applicant will contribute readily to the main research programme of the host laboratory, the understanding of the mechanism of the maturation of Fe/S proteins.