Iron solutions: acquisition strategies and signaling pathways in plants Wolfgang Schmidt University of Oldenburg, Department of Biology, PO Box 2503, 26111 Oldenburg, Germany Iron is an essential nutrient for plants and crucial for a variety of cellular functions. In most soils, iron is pre- sent in large quantities, but mainly in forms that are not available to plants. Mobilization of iron by plants is achieved by different strategies, either by secretion of plant-borne chelators or by reductive and proton- promoted processes. These reactions, and subsequent uptake of Fe via specific transporters, are increased when the Fe requirements of the plant are not being met. When iron is taken up in excess of cellular needs, toxic oxygen radicals can form. Therefore, plants must tightly regulate iron levels within the cell. This article presents recent progress towards an integrative picture of how iron is sensed and acquired. Although abundant at the Earth’s crust, iron is extremely insoluble in oxic (oxygenated) environments, being mainly present as oxihydrates with low bioavailability. As a further constraint, high levels of bicarbonate often decrease the activity of Fe species far below that required by plants. Because of its fundamental role in many vital processes, organisms have evolved mechanisms that transform iron into forms that can be used by cells. In plants, most of the components involved in iron acquisition and uptake have been characterized at the molecular level during the past few years, and microarray analysis of iron- inducible genes have provided insights into global changes in the metabolism of plants in response to the nutritional status [1–3]. However, elucidation of the regulatory control underlying these changes in gene expression and enzyme activity is still in its infancy. Uptake of iron according to the demand of the plant requires mechanisms that can sense and respond to changes in iron levels, either within the cell or in its immediate environment. The evolution of multicellular plants made the regulation more complex; in vascular plants, responses that integrate the requirement of different tissues or organs at different developmental stages are necessary to enable an adequate supply. In higher plants, uptake rates are correlated with the requirement of the shoot rather than with the iron concentration of the cells that mediate uptake [4]. Such behavior is indicative of the involvement of a transloca- table signal communicating the iron status between the shoot and the roots. Cloning of the first genes with putative roles in iron signaling has begun to unravel the nature of the sensor(s) and its downstream targets in plants at a molecular level [3,5,6], but most pieces of the puzzle are still missing. Not only plants suffer from iron deficiency. About two- thirds of the world’s population is at risk of iron-deficiency- induced anemia (http://www.who.int/nut/ida.htm), the most prevalent nutrient-related human disease. Because plants are the primary source of iron for humans, under- standing the mechanisms that underlie iron homeostasis is of interest for addressing agricultural problems and iron malnutrition of humans. Beside these important conse- quences, the complex regulation of iron nutrition in plants represents a fascinating series of adaptations to a limited resource. Strategies for iron acquisition in plants Incorporation of iron into cellular constituents such as heme and iron – sulfur clusters requires the reduction of ferric iron to its ferrous form. Depending on the phylo- genetic origin of the species, this process takes place either outside the cell or within the cytoplasm. In grasses (Poaceae), after forming a complex with plant-borne high-affinity Fe(III) chelators (phytosiderophores, PS), iron is taken up by a transporter specific for the Fe(III) siderophore complex (strategy II) (Fig. 1) [7]. A transporter mediating the uptake of PS has recently been identified [8]. Splitting of the chelate, by ligand exchange or some other mechanisms, occurs within the cell. All other higher plants reduce ferric iron before uptake (strategy I) (Fig. 1), a process that is mediated by a plasma membrane-bound redox system. Analysis of mutants defective in ferric chelate reductase activity has proven that this step is essential for iron acquisition [9]. Sequence similarities with the yeast Fe reductase FREp enabled a plant ferric chelate reductase named FRO2 (ferric reductase oxidase) from Arabidopsis to be cloned [10]. An ortholog of FRO2, named FRO1, has recently been cloned from pea [11]. Mobilization, uptake and sequestration In strategy I plants, iron mobilization is achieved by the combined action of a proton-extruding H þ -ATPase and a ferric chelate reductase, both enzymes being induced by iron deficiency [10,12]. In addition, the patterning of epidermal root cells is characteristically altered by iron availability, thereby increasing the absorptive surface area of the roots. For example, root hair density is significantly increased in response to iron shortage [13]. In some species, a specialized cell type referred to as transfer cells is induced in the rhizodermis. These cells are Corresponding author: Wolfgang Schmidt (wolfgang.schmidt@uni-oldenburg.de). Review TRENDS in Plant Science Vol.8 No.4 April 2003 188 http://plants.trends.com 1360-1385/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S1360-1385(03)00048-7