**Conflict of interest**

could be another mechanism evolved by cyanobacteria related to iron homeostasis, on track to survive in iron-limited conditions. In agreement with this statement, it was shown that in *M. aeruginosa* PCC 7806, the *mcy* operon was regulated by Fur [124], and that the *mcy* operon transcription as well as microcystin content were enhanced under iron-limited conditions [172]. Recently, microcystin ability to bind iron and other metals has been demonstrated using various experimental approaches [171], corroborating a possible role of this molecule in iron metabolism. A putative role of microcystin acting as iron chelator involved in iron acquisition has been recurrently suggested. The main problem associated to this theory is the fact that microcystin seems to be an endotoxin although the results showed in bibliography are contradictory. When radioactive inorganic carbon is supplied to *M. aeruginosa* and the fate of intracellular microcystin pool is followed, no export of microcystin was observed [173]. However, the *mcyH* gene included in the *mcy* operon encoded an ABC transporter reported to be essential for microcystin synthesis, suggesting a possible export of microcystin outside of the cell [174]. On the other hand, electron microscopy of immuno-gold labeled microcystin showed that the vast majority of intracellular microcystin is located around the thylakoids [175–177]; hence, a possible role in protecting the photosynthetic machinery to photo-oxidation has been proposed. Recently, it has been described that microcystin can perform metal-driven oligomerization. Some environmental stresses such as low iron or high light conditions cause oxidative stress in the cell which triggers photo-oxidation phenomena. In this scenario, the PSs can be disassembly and then, microcystin could perform oligomerization and capture of iron avoiding metal-dependent Fenton reactions [171]. Another proposed role is related with colony formation performed by *Microcystis* cells. Solid evidences linking microcystin pres-

ence and enhanced colony formation and size have been reported [178].

Iron is at the core of cyanobacterial metabolic and regulatory networks, playing a central role in the control of electron delivery and distribution in the photosynthetic and respiratory electron transport chains, the reduction of nitrogenase and central metabolic pathways. The adaptive responses of cyanobacteria to iron limitation affect all those processes, though the iron demand of the cell is subject to a hierarchy in favor of photosynthesis. The high quota of iron in cyanobacteria, its ability to promote oxidative stress and its ubiquity in electron transport pathways require a tight control of iron homeostasis mainly performed by FurA. In order to optimize iron resources, the regulation of FurA activity and expression, as well as the genes composing the FurA regulon are strongly interconnected with other master regulators

This work has been supported by grants B18 from Gobierno de Aragón, BFU2012-31458/FEDER & BFU2016-77671-P/FEDER from MINECO and UZ2016-BIO-02 from University of Zaragoza.

**7. Conclusion**

124 Cyanobacteria

such as PerR and NtcA.

**Acknowledgements**

The authors declare no conflicts of interest.
