Steps Toward Understanding Mitochondrial Fe/S Cluster Biogenesis

Iron-sulfur clusters (Fe/S clusters) are essential cofactors required throughout the clades of biology for performing a myriad of unique functions including nitrogen fixation, ribosome assembly, DNA repair, mitochondrial respiration, and metabolite catabolism. Although Fe/S clusters can be synthesized in vitro and transferred to a client protein without enzymatic assistance, biology has evolved intricate mechanisms to assemble and transfer Fe/S clusters within the cellular environment. In eukaryotes, the foundation of all cellular clusters starts within the mitochondria. The focus of this review is to detail the mitochondrial Fe/S biogenesis (ISC) pathway along with the Fe/S cluster transfer steps necessary to mature Fe/S proteins. New advances in our understanding of the mitochondrial Fe/S biogenesis machinery will be highlighted. Additionally, we will address various experimental approaches that have been successful in the identification and characterization of components of the ISC pathway.