Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms

McQuaid, JB, Kustka AB, Oborník M, Horák A, McCrow JP, Karas BJ, Zheng H, Kindeberg T, Andersson AJ, Barbeau KA, Allen AE.  2018.  Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms. Nature. 555:534.: Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

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In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton1,2. Although most dissolved iron in the marine environment is complexed with organic molecules3, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone4 and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms5. Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts6,7, including the ferric iron-concentrating protein ISIP2A8, but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum, and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum, the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron uptake. Phytotransferrin sequences have a broad taxonomic distribution8 and are abundant in marine environmental genomic datasets9,10, suggesting that acidification-driven declines in the concentration of seawater carbonate ions will have a negative effect on this globally important eukaryotic iron acquisition mechanism.