European Worm Meeting,
Iron-sulfur clusters (ISC) are co-factors of numerous proteins with important functions in metabolism, electron transport and regulation of gene expression. Biosynthesis of these proteins is a complex process involving numerous components. In eukaryote cells, this process is accomplished inside mitochondria. The mitochondrial ISC machinery is responsible for biogenesis iron-sulfur proteins both within and outside the organelle. Fe/S cluster biosynthesis for the model eukaryote Saccharomyces cerevisiae is initiated by the abstration of sulfur from cysteine in a reaction catalysed by cysteine desulfurase (Nfs1). For this reduction electrons are needed that are transferred by an electron transport chain encompassing the adrenodoxin reductase Arh1p and ferredoxin Yah1p. Fe/S assembly is mediated by protein Isu1/Isu2, Isa1/Isa2 and Nfu1. Maturation of the latter proteins involves the ABC transporter Atm1p which presumably exports iron-sulfur clusters from the mitochondria towards cytosol. We are addressing the analysis of ISC metabolism in mitochondria by genetic studies in C. elegans. Genes orthologues of the proteins involved in the ISC biogenesis of were searched in C.elegans for homology to the genes already described in S.cerevisiae. These genes are Y45F10D.4, Y39B6A.3, R10H10.1, Y73F8A.27, B0205.6, Y62E10A.6 and Y74C10AM.1 that show homology to the genes of S.cerevisiae Isu1/Isu2, Isa1/Isa2, Nfu1, Yah1, Nfs1, Arh1 and Atm1 respectively. Transient knock-down experiments by RNAi produce a specific phenotype in worms of the F1 generation. All knock-down mutants have a common phenotype: embryonic lethality or/and larva arrest (Lva) and slow growth (Gro). Moreover, some knock-down mutans of R10H10.1 and Y74C10AM.1 were able to get the size of adult worm. In this case it was possible to measure defecation rhythm and life span. Knock-down mutant of R10H10.1 shows life span longer (p<0.05) than in wild-type. Knock-down mutant of Y74C10AM.1 has a high reduction of the defecation rhythm (p<0.05) and the life span is increased (p<0.05).