Ancestral Iron Metabolism

Finoshin, A.D. et al (Iron in the processes of sponge plasticity PLoS ONE · Feb 2020 DOI: 10.1371/journal.pone.0228722)

Although iron has been proposed to have played a pivotal role in life since its inception, few studies have dealt with iron metabolism in ancestral invertebrates.  In a recent publication Finoshin et al (2020) investigated ironmetabolic pathways in White Sea cold water sponges, the oldest animal phylum that have unique structural plasticity and capacity to re-aggregate after complete dissociation. The sea-water sponges undergo severe tissue reorganizations during their life-cycle, and degenerative and regenerative phenomena are associated with sexual and asexual reproduction. The reaggregation process which begins in the sponge cell suspension immediately after the body dissociation depends on iron availability, a feature that is also reflected in dramatic changes in the expression of genes encoding proteins of iron metabolic pathways.

In this work the authors examined molecular features that accompany dissociation and reaggregation using de novo transcriptomes that were assembled using RNA-Seq data, and analyzed evolutionary trends with bioinformatic tools. They observed that:

1. The classical proteins of iron metabolism that are present in more distant classes of invertebrates and mammals are not detected in sponges:  e.g. ferritin light chain, the ferrous iron transporter Zip14, the metal reductase transporters Dcytb and STEAP2 / 3 , Ceruloplasmin, Hephaestin (Intestinal and ferroxidase) IRP2 mitochondrial transporter ABCB10, Hepcidin , Hemojuvelin,  Tf and Tfr1 / 2 (although the Tfr1/2 family is represented in sponges by an ancient homolog, NAALAD2

2. in the course of body dissociation,  oxygenation of sponge cells evokes a decrease in the expression of ferritin FTH1 and most of the genes connected to the heme biosynthesis and hypoxic response, whereas

3. in the course of reaggregation, they found: a.  differential expression patterns of enzymes of the heme biosynthetic pathway and transport globins; b. increased expression of IRP1, the antiapoptotic factor BCL2, the inflammation factor NFκB (p65), FTH1 (ferritin heavy chain) and NGB (neuroglobin), and c. an increase in mitochondrial density. The authors suggest that the induction of globin NGB expression in aggregating cells and the marked increase in mitochondrial density reflect a high demand for energy in the reaggregation process. The increased expression of IRP1 was implicated in terms of coordinated regulation of translation of the key mRNAs of ferritin (FTH1) and a putative transferrin receptor analog NAALAD2.  In fact, they detected 25 IREs in the mRNAs of sponge proteins involved in iron metabolism: 9 IREs located in the 5´ UTRs of mRNAs, 10 in IREs located in the 3´ untranslated regions and 8 IREs in the coding regions of mRNAs.

As the expression of IRP1 markedly increases under the aggregation of dissociated cells, it might implicate IRP1 in the regulation of sponge morphogenesis and the IRP-IRE regulatory system in early evolutionary development of metazoans. However, how does the parallel increase of IRP1 and FTH1 expression during re-aggregation fit with the proposed role of FT in protecting cells from potential toxic effects of labile iron remains unclear. The same functional uncertainty pertains to the expression patterns of three HIFa homologs during dissociation/reaggregation processes.

It is hoped that with proteomic analysis, the dramatic changes in the expression of genes encoding proteins of iron metabolic pathways found during dissociation-reaggregation of sponges, the role of iron metabolism in animal differentiation will be firmly established.

Ioav Cabantchik

 Feb 2020