Conservative and Atypical Ferritins of Sponges.

Kim I Adameyko,Kirill V Mikhailov,Pavel A Erokhov,Alexander D Finoshin,Nicolay G Gornostaev,Maria I Indeykina,Irina V Zhegalova,Olga Sokolova ,A V Burakov ,Victor S Mikhailov ,Artem Bonchuk ,Oleg Gusev ,А Е Бугрова ,А С Кононихин ,Anton Georgiev ,О С Козлова ,О И Кравчук ,Elena Shagimardanova ,Andrey Moiseenko ,Natalia Gogoleva ,Alexander Cherkasov ,Guzel Gazizova ,Yu V Lyupina

doi:10.3390/ijms22168635

Abstract

Ferritins comprise a conservative family of proteins found in all species and play an essential role in resistance to redox stress, immune response, and cell differentiation. Sponges (Porifera) are the oldest Metazoa that show unique plasticity and regenerative potential. Here, we characterize the ferritins of two cold-water sponges using proteomics, spectral microscopy, and bioinformatic analysis. The recently duplicated conservative HdF1a/b and atypical HdF2 genes were found in the Halisarca dujardini genome. Multiple related transcripts of HpF1 were identified in the Halichondria panicea transcriptome. Expression of HdF1a/b was much higher than that of HdF2 in all annual seasons and regulated differently during the sponge dissociation/reaggregation. The presence of the MRE and HRE motifs in the HdF1 and HdF2 promotor regions and the IRE motif in mRNAs of HdF1 and HpF indicates that sponge ferritins expression depends on the cellular iron and oxygen levels. The gel electrophoresis combined with specific staining and mass spectrometry confirmed the presence of ferric ions and ferritins in multi-subunit complexes. The 3D modeling predicts the iron-binding capacity of HdF1 and HpF1 at the ferroxidase center and the absence of iron-binding in atypical HdF2. Interestingly, atypical ferritins lacking iron-binding capacity were found in genomes of many invertebrate species. Their function deserves further research.

Highlights

Regulation of iron availability is an important part of cellular homeostasis
hypoxia response element (HRE) motifs found in upstream regions of HdF1a and HdF2 (i.a. within CpG islands) presumably make them sensitive to hypoxia [15]; in turn, we have previously shown that hypoxic response is important for sponge reaggregation process [24]
We suggest that ferritins of H. dujardini and H. panicea are secreted from cells by a non-classical endosome secretion pathway

Summary

Introduction

Regulation of iron availability is an important part of cellular homeostasis. The bioavailability of iron is limited by the insolubility of ferric salts, while the excess of free iron leads to oxidative stress. A decrease in H-ferritin can induce epithelial-to-mesenchymal transition of mammalian tumor cells through the TGF- β1 pathway [12,13,14]. Cell death by ferroptosis is characterized by the iron-dependent accumulation of reactive oxidized lipid species and depends on the regulation of iron storage and ferritin expression [16]. The most specialized mammalian cells which are highly sensitive to iron deficiency and ferroptosis are the neural cells [18]. They utilize excessive iron under certain conditions (magnetic resonance imaging) faster than other body cells [19]. Exploring the functions of ferritins in ancient animals is of special interest

Methods

Results

Discussion

Conclusion