Protein networks in the maturation of human iron-sulfur proteins.

The biogenesis of iron-sulfur (Fe-S) proteins in humans is a multistage process occurring in different cellular compartments. The mitochondrial iron-sulfur cluster (ISC) assembly machinery composed of at least 17 proteins assembles mitochondrial Fe-S proteins. A cytosolic iron-sulfur assembly (CIA) machinery composed of at least 13 proteins has been more recently identified and shown to be responsible for the Fe-S cluster incorporation into cytosolic and nuclear Fe-S proteins. Cytosolic and nuclear Fe-S protein maturation requires not only the CIA machinery, but also the components of the mitochondrial ISC assembly machinery. An ISC export machinery, composed of a protein transporter located in the mitochondrial inner membrane, has been proposed to act in mediating the export process of a still unknown component that is required for the CIA machinery. Several functional and molecular aspects of the protein networks operative in the three machineries are still largely obscure. This Review focuses on the Fe-S protein maturation processes in humans with the specific aim of providing a molecular picture of the currently known protein-protein interaction networks. The human ISC and CIA machineries are presented, and the ISC export machinery is discussed with respect to possible molecules being the substrates of the mitochondrial protein transporter.