Abstract:Iron, an essential nutrient for the survival of virtually all living organisms, participates in a variety of important biological processes mainly in the form of protein cofactors. For bacteria, iron shortage is a severe challenge to overcome and iron overload imposes an equally critical threat. The dualistic properties of iron prompt bacterial cells to carefully maintain intracellular iron homeostasis. Current mechanic model for iron homeostasis in gram-negative bacteria is mainly derived from the extensive studies of model bacterium Escherichia coli. In recent years, investigations into iron homeostasis in environmental bacteria have revealed surprising diversities in iron-controlling mechanisms among gram-negative bacteria. With respect to iron homeostasis, the biological pathways and their components, major regulators and their physiological impacts, and interactions between iron homeostasis and other physiological activities display a myriad of species-specific characteristics formed by evolution. This review, stemming from the discoveries in Shewanella, summarizes recent advances about the biological processes involved in iron homeostasis, their reciprocal influences, and physiological consequences of imbalanced iron homeostasis due to altered regulation, as well as lists out the questions to be addressed, aiming at facilitate future explorations in the field of iron homeostasis.