Authors: Isabelle Michaud‐Soret | Sabeeha Merchant | Benoît D’Autréaux
Source:  (article, 2025-10-07)
Field: Chemistry — Inorganic Chemistry

19th international Biometals Webinars iBWs Introduction to the 19th international Biometals Webinars Algal responses to poor Fe nutrition The green algae share an evolutionary history with land plants, which means that discoveries in one system inform our understanding of the other, especially in the context of photosynthesis and chloroplast biology. Dunaliella spp. are halotolerant extromephiles and have long been cultivated for valuable bioproducts. Systems analysis of Fe-deficiency in two divergent species from the Sinai peninsula (D. salina) or Oslofjord (D. tertiolecta) indicated novel mechanisms of Fe-acquisition and sparing and suggested compositional variation in photosystem I, which motivated structural analysis, revealing a unique pattern of antenna organization. This work was contributed by Helen Liu, Radhika Khera and Masa Iwai. Iron-sulfur clusters biogenesis: in the intimacy of iron and sulfur encounter, their assembly and the regulation of their production Iron-sulfur (Fe-S) cluster are ubiquitous prosthetic groups of proteins constituting the active sites of enzymes performing essential biochemical reactions in electron transfer, catalysis, sulfur donation and signaling for numerous cellular processes including ATP production, the Krebs cycle, the functionalization of biomolecules, protein and DNA synthesis and the maintenance of genome integrity. They are biosynthesized by multi-protein machineries as [2Fe-2S] clusters which are the building blocks to assemble [4Fe-4S] clusters. These machineries have been highly conserved during evolution. In eukaryotes, except plants, their synthesis exclusively relies on the ISC machinery which is present in mitochondria which and was inherited from a bacterial ancestor. In mitochondria, [2Fe-2S] clusters are assembled on a scaffold protein named ISCU2. The reaction is initiated by Fe2+ binding to ISCU2, which enables sulfur acquisition in the form of a cysteine-bound persulfide provided by the cysteine desulfurase NFS1. This transfer reaction is accelerated by the frataxin protein FXN. The persulfide in ISCU2 is then cleaved into sulfide by the ferredoxin FDX2 and its cognate reductase FDXR, which leads to formation of a [2Fe-2S] cluster. Despite several decades of research is still unclear how the iron and sulfide ions are assembled to generate a [2Fe-2S] cluster. I will report recent data on the isolation and characterization of keys intermediates of the [2Fe-2S] clusters assembly process by a bacterial ISC machinery from Escherichia coli using an in vitro reconstituted system with purified proteins and an array of biochemical and biophysical approaches (persulfide detection assays, CD, EPR and UV-visible spectroscopies, native mass spectrometry). The data reveal that [2Fe-2S] clusters assembly relies on the fusion of [1Fe-1S] precursors. We found that this mechanism most likely also applies to the eukaryotic system. I will also present data on the regulation of [2Fe-2S] clusters synthesis by FXN in the human ISC machinery, with implications for the rare disease Friedreich’s ataxia (FA). FA is a neurodegenerative and cardiac disease caused by defective expression of FXN. We have uncovered antagonistic roles of FXN and FDX2 in [2Fe-2S] clusters synthesis which enable a fine tuning of Fe-S cluster synthesis depending on the ratio of both proteins. Context (archaeology) ; Genome ; Photosynthesis ; Chloroplast ; Algae ; Photosystem I ; Scaffold protein Radioactive element chemistry and processing ; Trace Elements in Health ; Analytical chemistry methods development