Parasites FeS Up: Iron-Sulfur Cluster Biogenesis in Eukaryotic Pathogens

Abstract

Iron-sulfur (FeS) clusters are among the most ancient and versatile protein cofactors. They are used by a large and diverse group of proteins, serving both structural and catalytic roles. They function in central metabolic processes such as electron transfer, redox chemistry, enzyme catalysis, and sensing environmental or intracellular conditions to regulate gene expression Ferrous iron and sulfur were readily available in the reducing atmosphere in which life first evolved, but when oxygen levels rose with the advent of photosynthetic algae, these building blocks became scarce. Furthermore, the reactive oxygen species generated as byproducts of aerobic respiration are highly damaging to FeS clusters, and free iron and sulfide released by FeS clusters are, in turn, toxic to cells. For these reasons, complex mechanisms evolved to coordinate and regulate the biogenesis of these simple cofactors, and these pathways are compartmentalized in the endosymbiotic organelles of eukaryotic cells.