Mechanism of gene activation by iron

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Iron (Fe) is a key nutrient for most organisms. This metal is universally present in the active site of iron-utilizing enzymes, which are involved in metabolic pathways such as the tricarboxylic acid (TCA) cycle, respiration, oxygen transport, DNA synthesis, and synthesis of metabolites. Although iron is one of the most abundant metals on earth, it is nearly inaccessible because of poor solubility in aerobic conditions at neutral pH. During growth under iron depletion conditions, bacteria secrete in their environment low-molecular weight molecules called siderophores (named enterobactin or enterochelin), which makes the iron soluble before it is transported inside the cell through iron acquisition proteins. Thus, when intracellular iron level is high, the protein Fur (Ferric uptake regulator) represses transcription initiation of iron uptake genes, with iron as a co-factor. In contrast with this, we have shown that transcription of several genes is activated under conditions of high intracellular iron, or in the presence of a specific small RNA. These genes, 15 in total, are grouped in 10 operons. Several of them are directly involved in iron metabolism (e.g. ferritin) while other have unknown function. This mechanism of iron-dependent transcriptional activation remains unclear. Our research program addresses the mechanism of activation of these genes as well as their functions.