The recruitment of Fe-S centers - entities made up of iron and sulfur atoms in a defined geometry - by proteins is probably very ancient and was facilitated by the abundance of these two elements on the Earth's surface when life first appeared. Proteins with Fe-S centers therefore play a crucial role in the biology of all living organisms today, and participate in all major cellular processes, from gene expression to DNA replication via ribosomal RNA modification, central metabolism or photosynthesis. However, this evolutionary success is not without its difficulties and constraints. One of these is the paradoxical relationship between Fe-S centers and oxygen (O2) and its derived active forms (FAO). Indeed, Fe-S centers are remarkable sensors of the presence of O2 or FAOs, enabling cells to adapt to the presence of the former and protect themselves from the latter.
However, Fe-S centers can be degraded by O2 and FAOs, or even contribute to the formation of FAOs(via Fenton chemistry), putting the cells that harbor them at risk. What molecular strategies are living organisms developing to continue exploiting the remarkable chemical and electronic properties of Fe-S centers, while controlling their fragility and potential toxicity? Another difficulty is linked to the scarcity of bio-available iron. How can Fe-S centers be constructed when iron is usually found in limiting concentrations? Another challenge is the abundance of Fe-S center proteins in an organism. For example, over 5% of the Escherichia coli proteome, or around 200 protein species, have one or more Fe-S centers.
How do living organisms manage the construction and distribution of Fe-S centers to meet the demands of this quantitatively and qualitatively important population? We have attempted to answer these questions by presenting our studies in Escherichia coli. The results of the chemistry, biochemistry, genetics and molecular physiology approaches we presented enabled us to lay the foundations for an integrated vision of Fe-S center protein biogenesis in a model organism.
