A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins

Iron-sulfur (Fe/S) cluster-containing proteins catalyze a number of electro n transfer and metabolic reactions. The components and molecular mechanisms involved in the assembly of the Fe/S clusters have been identified only pa rtially. In eukaryotes, mitochondria have been proposed to execute a crucia l task in the generation of intramitochondrial and extramitochondrial Fe/S proteins. Herein, we identify the essential ferredoxin Yah1p of Saccharomyc es cerevisiae mitochondria as a central component of the Fe/S protein biosy nthesis machinery. Depletion of Yah1p by regulated gene expression resulted in a 30-fold accumulation of iron within mitochondria, similar to what has been reported for other components involved in Fe/S protein biogenesis, Ya h1p was shown to be required for the assembly of Fe/S proteins both inside mitochondria and in the cytosol. Apparently, at least one of the steps of F e/S cluster biogenesis within mitochondria requires reduction by ferredoxin . Our findings lend support to the idea of a primary function of mitochondr ia in the biosynthesis of Fe/S proteins outside the organelle, To our knowl edge, Yah1p is the first member of the ferredoxin family for which a functi on in Fe/S cluster formation has been established. A similar role may be pr edicted for the bacterial homologs that are encoded within iron-sulfur clus ter assembly (isc) operons of prokaryotes.