Shipping iron around in small packages: Iron plays a crucial role in a wide variety of biological functions, which in turn rely on the proteins that transport the metal in and out of cells. Grillo et al. used a simple lipophilic small molecule that binds iron ions to restore transport in animal models with deficiencies in iron transporters. This cyclic ketol, hinokitiol, was first tested in yeast and then shown to promote gut iron absorption in rats and mice, as well as hemoglobin production in zebrafish. Science , this issue p. 608

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate the uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is the ligation of the iron–sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. FeS clusters that function as biological sensors have been implicated in a diverse group of life from mammals to bacteria, fungi, plants, and archaea. Here, we will explore the ways in which cells and organisms utilize Fe-S clusters to sense changes in their intracellular environment and restore equilibrium.

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.