LAUSR

Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein– protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins (see the Chapter “Mammalian iron sulfur cluster biogenesis; from assembly to delivery to recipient proteins with a focus on novel targets of the chaperone and co-chaperone proteins”). Here, we concisely outline the molecular pathways that assemble [4Fe-4S] clusters in mitochondria through the involvement of the secondary carriers GLRX5, ISCA1, ISCA2, BOLA3, IBA57, and NFU1, all of which are essential for human physiology, as mutations in any of the genes that encode these components of the Fe-S biogenesis pathway cause distinctive phenotypes of rare human diseases, which will also be covered in this chapter. 2 | DISTINCT PATHWAYS ASSEMBLE [4FE-4S] CLUSTERS IN MITOCHONDRIA FOR SPECIFIC FE-S RECIPIENT PROTEINS