Biogenesis of iron–sulfur proteins in eukaryotes: components, mechanism and pathology

Abstract

Iron–sulfur (Fe–S) clusters are ubiquitous co-factors of proteins that play an important role in metabolism, electron-transfer and regulation of gene expression. In eukaryotes mitochondria are the primary site of Fe–S cluster biogenesis. The organelles contain some ten proteins of the so-called iron–sulfur cluster (ISC) assembly machinery that is well-conserved in bacteria and eukaryotes. The ISC assembly machinery is responsible for biogenesis of Fe–S proteins within mitochondria. In addition, this machinery is involved in the maturation of extra-mitochondrial Fe–S proteins by cooperating with mitochondrial proteins with an exclusive function in this process. This review summarizes recent developments in our understanding of the biogenesis of cellular Fe–S proteins in eukaryotes. Particular emphasis is given to disorders in Fe–S protein biogenesis causing human disease.