Nicotianamine: A Key Player in Metal Homeostasis and Hyperaccumulation in Plants

Abstract

Nicotianamine (NA) is a low-molecular-weight N-containing metal-binding ligand, whose accumulation in plant organs changes under metal deficiency or excess. Although NA biosynthesis can be induced in vivo by various metals, this non-proteinogenic amino acid is mainly involved in the detoxification and transport of iron, zinc, nickel, copper and manganese. This review summarizes the current knowledge on NA biosynthesis and its regulation, considers the mechanisms of NA secretion by plant roots, as well as the mechanisms of intracellular transport of NA and its complexes with metals, and its role in radial and long-distance metal transport. Its role in metal tolerance is also discussed. The NA contents in excluders, storing metals primarily in roots, and in hyperaccumulators, accumulating metals mainly in shoots, are compared. The available data suggest that NA plays an important role in maintaining metal homeostasis and hyperaccumulation mechanisms. The study of metal-binding compounds is of interdisciplinary significance, not only regarding their effects on metal toxicity in plants, but also in connection with the development of biofortification approaches to increase the metal contents, primarily of iron and zinc, in agricultural plants, since the deficiency of these elements in food crops seriously affects human health.

Keywords: copper; iron; manganese; metal accumulation in plants; metal detoxification; metal homeostasis; metal remobilization; metal transport; nickel; nicotianamine; stress; zinc.

Figure 1

The role of nicotianamine in metal uptake, transport and detoxification in plants. The synthesis of nicotianamine (NA) from methionine is carried out in two steps involving the enzymes S-adenosylmethionine synthetase and nicotianamine synthetase, the latter being present not only in the cytosol but also in various organelles. The NA produced in the rhizodermal cells can be secreted into the rhizosphere via the efflux transporter of NA (ENA1). This is followed by the formation of complexes with metals (Me). In cereals, Me–NA complexes can be taken up by yellow stripe-like (YSL) transporters. Me–NA complexes formed in the cytosol of root rhizodermal and cortical cells can be transported towards the central cylinder, which limits metal entry into the vacuoles of root cells and plays an important role in the mechanism of hyperaccumulation (shown by arrows highlighted in red). Nicotianamine can be transported across the tonoplast via the zinc-induced facilitator 1 (ZIF1) transporter and is probably partially involved in metal binding inside the vacuole, although the stability of NA complexes with metals at the vacuolar sap pH is low. The loading of the Me–NA complexes into the xylem is carried out by YSL transporters. In addition, NA, as a symplastic chelator, can carry out metal delivery to a transporter, e.g., Zn to the P_1B-type ATPase HMA4. It has been suggested that NA can enter the xylem via the ENA transporter, but this requires further confirmation. In the xylem sap, due to the low pH value, Me–NA complexes are not stable and are partially degraded, and metals bind to organic acids (OAs), forming, for example, citrates and malates. Nicotianamine-dependent metal loading into the phloem in non-graminaceous species occurs with the participation of NA efflux transporters 1/2 (NAET1/2), which provide NA entry into secretory vesicles. Then, NA is secreted through exocytosis into the apoplastic space, where it forms Me–NA complexes, which are subsequently loaded into the phloem via the YSL transporter. In cereals, a similar mechanism involving 2′-deoxymugineic acid, which is synthesized from NA in mugineic acid (MA) vesicles, may function. The stability of Me–NA complexes in the phloem sap is higher than that in the xylem sap due to the higher pH values in the former. As a result, NA participates in long-distance metal transport mainly via the phloem.