The first hints for the primary involvement of frataxin in Fe-S cluster biogenesis came from the characterization of the cardiac mouse model mimicking the FRDA cardiomyopathy, as Fe-S cluster dependent enzymes were affected prior to the appearance of the heart dysfunction and the mitochondrial iron accumulation (Puccio et al., 2001; Seznec et al., 2004; Martelli et al., 2007) (Figure 3A). Here, FXN is linked to Friedreich ataxia.