The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis ofcytosolic Fe/S proteins

Iron-sulfur (Fe/S) cluster-containing proteins catalyse a number of electro n transfer and metabolic reactions. Little is known about the biogenesis of Fe/S clusters in the eukaryotic cell. Here, we demonstrate that mitochondr ia perform an essential role in the synthesis of both intra- and extra-mito chondrial Fe/S proteins. Nfs1p represents the yeast orthologue of the bacte rial cysteine desulfurase NifS that initiates biogenesis by producing eleme ntal sulfur. The matrix-localized protein is required for synthesis of both mitochondrial and cytosolic Fe/S proteins. The ATP-binding cassette (ABC) transporter Atm1p of the mitochondrial inner membrane performs an essential function only in the generation of cytosolic Fe/S proteins by mediating ex port of Fe/S cluster precursors synthesized by Nfs1p and other mitochondria l proteins, Assembly of cellular Fe/S clusters constitutes an indispensable biosynthetic task of mitochondria with potential relevance for an iron-sto rage disease and the control of cellular iron uptake.