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Synthesis and assembly of iron-sulphur (Fe/S) clusters into target proteins is a highly complex, coordinated and conserved process in living cells. Several machineries in both bacteria and eukaryotes have been discovered to assist Fe/S protein maturation. The importance of Fe/S proteins for human life and the comprehension at the molecular and cellular level of their biogenesis is documented by an increasing number of diseases linked to functional impairment of these proteins and of their maturation processes. Many of these diseases are fatal, sometimes in early childhood, which is not surprising based on the essential needs of Fe/S proteins in cellular metabolism. The founding member of Fe/S diseases is the neurodegenerative disorder Friedreich’s ataxia, in which the protein Frataxin is functionally deficient, either by a more than 70% decrease in protein levels as a result of decreased transcription or by point mutations. This functional impairment is associated with decreased activities of respiratory complexes I–III and of mitochondrial Aconitase