Molecular characteristics of proteins within the mitochondrial Fe-S cluster assembly complex

Iron-Su l f u r (Fe-S) clusters are essential for life, as they are widely utilized in nearly ever y biochemical pathway. When bound to proteins, Fe-S clusters assist in catalysis, signal recognition, and ener g y transfer events, as we l l as additional cellular pathways including cellular respiration and DNA repair and replication. In Eukaryotes, Fe-S clusters are produced through coordinated activity by mitochondrial Iron-Sul f u r Cluster (ISC) assembly pathway proteins through direct assembly, or through the production of the activated su l f u r substrate used by the Cytosolic Iron-Su l f u r Cluster Assembly (CIA) pathway. In the mitochondria, Fe-S cluster assembly is accom-plished through the coordinated activity of the ISC pathway protein complex composed of a cysteine desulfurase, a scaffold protein, the accessory ISD11 protein, the acyl carrier protein, frataxin, and a ferredoxin; downstream events that accomplish Fe-S cluster transfer and delive r y are driven by additional chaperone/delive r y proteins that interact with the ISC assembly complex. Deficiency in human production or activity of Fe-S cluster con-taining proteins is often detrimental to ce l l and organism viability. Here we summarize what is known about the structure and functional activities of the proteins involved in the early steps of assembling [2Fe-2S] clusters before they are transferred to proteins devoted to their delivery. Ou r goal is to provide a comprehensive overview of how the ISC assembly apparatus proteins interact to make the Fe-S cluster which can be delivered to proteins downstream to the assembly event.

Automated summary

Fe-S clusters play crucial roles in biochemical pathways in living organisms, synthesizing through mitochondrial and cytosolic pathways in eukaryotes. Deficiency in Fe-S clusters can be detrimental to cell and organism viability.