The essential role of mitochondria in the biogenesis of cellular iron-sulfur proteins

Iron-sulfur (Fe/S) proteins play an important role in electron transfer pro cesses and in various enzymatic reactions, In eukaryotic cells, known Fe/S proteins are localised in mitochondria, the cytosol and the nucleus. The bi ogenesis of these proteins has only recently become the focus of investigat ions, Mitochondria are the major site of Fe/S cluster biosynthesis in the c ell. The organelles contain an Fe/S cluster biosynthesis apparatus that res embles that of prokaryotic cells. This apparatus consists of some ten prote ins including a cysteine desulfurase producing elemental sulfur for biogene sis, a ferredoxin involved in reduction, and two chaperones, The mitochondr ial Fe/S cluster synthesis apparatus not only assembles mitochondrial Fe/S proteins, but also initiates formation of extra-mitochondrial Fe/S proteins . This involves the export of sulfur and possibly iron from mitochondria to the cytosol, a reaction performed by the ABC transporter Atm Ip of the mit ochondrial inner membrane. A possible substrate of Atm1p is an Fe/S cluster that may be stabilised for transport. Constituents of the cytosol involved in the incorporation of the Fe/S cluster into apoproteins have not been de scribed yet. Many of the mitochondrial proteins involved in Fe/S cluster fo rmation are essential, illustrating the central importance of Fe/S proteins for life. Defects in Fe/S protein biogenesis are associated with the abnor mal accumulation of iron within mitochondria and are the cause of an iron s torage disease.