Abstract
Iron is an essential metal for almost all living organisms. The major 'consumers' of intracellular iron content are a group of proteins that require an iron-sulfur cluster for their functions. It has been shown that iron-sulfur clusters in proteins are assembled by a set of highly conserved proteins using intracellular free iron and L-cysteine as iron and sulfide sources, respectively. Ironically, excess iron is detrimental to cells as free ferrous iron promotes the production of reactive oxygen species via the Fenton reaction. In Escherichia coli, intracellular iron homeostasis is regulated primarily by a global transcription factor Fur (ferric uptake regulator). Since its discovery, it had been assumed that Fur binds ferrous iron to regulate intracellular iron homeostasis, oxidative stress response, and bacterial virulence, among others. However, the proposed 'iron-bound' Fur had never been identified in E. coli or any other bacteria. Recent studies have revealed that E. coli Fur binds a unique [2Fe-2S] cluster in response to elevation of intracellular free iron content, and that the [2Fe-2S] cluster in Fur is enzymatically assembled by the iron-sulfur cluster biogenesis machinery. Because Fur also regulates the expression of the genes encoding the iron-sulfur cluster assembly machinery, Fur represents a key link between biogenesis of iron-sulfur clusters and regulation of intracellular iron homeostasis in bacteria.