Copper and iron homeostasis in Arabidopsis: responses to metal deficiencies, interactions and biotechnological applications

Abstract

Plants have developed sophisticated mechanisms to tightly control the acquisition and distribution of copper and iron in response to environmental fluctuations. Recent studies with Arabidopsis thaliana are allowing the characterization of the diverse families and components involved in metal uptake, such as metal-chelate reductases and plasma membrane transporters. In parallel, emerging data on both intra-and intercellular metal distribution, as well as on long-distance transport, are contributing to the understanding of metal homeostatic networks in plants. Furthermore, gene expression analyses are deciphering coordinated mechanisms of regulation and response to copper and iron limitation. Prioritizing the use of metals in essential versus dispensable processes, and substituting specific metalloproteins by other metal counterparts, are examples of plant strategies to optimize copper and iron utilization. The metabolic links between copper and iron homeostasis are well documented in yeast, algae and mammals. In contrast, interactions between both metals in vascular plants remain controversial, mainly owing to the absence of copperdependent iron acquisition. This review describes putative interactions between both metals at different levels in plants. The characterization of plant copper and iron homeostasis should lead to biotechnological applications aimed at the alleviation of iron deficiency and copper contamination and, thus, have a beneficial impact on agricultural and human health problems.

Transition metal transport

“…A chelator that appears to have an important role in metal hyperaccumulation is nicotianamine (NA), which is synthesized from three molecules of S-adenosyl-L L-methionine by nicotianamine synthase (NAS) and can form complexes with several divalent metal cations [63]. Physiologically, NA has been linked with Fe and Cu, but also Ni and Zn homeostasis, and is involved in maintaining the mobility of metal ions in vascular tissues and between cells [2,16,63].…”

“…Finally, putative transporters of metal ion ligands, the AtFRD3 (Ferric Reductase Defective 3) of the large multidrug and toxin efflux (MATE) family and AtZIF1 (Zinc Induced Facilitator 1) of the major facilitator superfamily (MFS), have key roles in iron and Zn homeostasis, respectively [11][12][13]. These plant metal transporter families and their biological roles have been reviewed by other authors recently [2,[14][15][16][17][18][19][20][21] (review Iron Transport, this issue).…”

Optimal copper supply is required for normal plant iron deficiency responses

“…These metals form the active sites in numerous enzymes involved in disparate processes, such as mitochondrial respiration, photosynthesis, oxidative stress protection, and various metabolic pathways. [1][2][3][4] Low metal concentration leads to deficiency and inefficiencies in metabolism, while too much causes metal toxicity. Consequences of metal toxicity are oxidative damage to cellular components, 5 or displacement of the correct metal from active sites in proteins.…”

The Cth2 ARE-binding Protein Recruits the Dhh1 Helicase to Promote the Decay of Succinate Dehydrogenase SDH4 mRNA in Response to Iron Deficiency

“…In fact, iron deficiency anemia represents the primary nutritional disorder in the world, estimated to affect over two billion people (1). Living organisms have developed sophisticated transcriptional and post-transcriptional mechanisms to optimize iron acquisition and utilization during scarcity (2)(3)(4)(5)(6).…”

“…Optimization of cellular iron utilization is coordinated by two additional Aft1/Aft2 targets: the RNA-binding proteins Cth1 and Cth2 (10,11). Cth1 and Cth2 proteins contain tandem CX 8 CX 5 CX 3 H-type zinc finger motifs responsible for binding to AU-rich elements (ARE) 5 located within the 3Ј-untranslated region (UTR) of target mRNAs, such as the succinate dehydrogenase subunit encoded by the SDH4 gene (10,11). In response to iron deficiency, Cth1 and Cth2 promote the degradation of many ARE-containing mRNAs encoding iron-binding proteins or enzymes that participate in metabolic pathways that use iron as a co-factor such as the tricarboxylic acid cycle, mitochondrial respiration, heme biosynthesis, and fatty acid synthesis (10).…”