Structural and functional characterization of the bacterial frataxin-like protein Nqo15

Friedreich ataxia (FRDA) is a cardio- and neurodegenerative disease caused by partial loss of the mitochondrial protein frataxin (FXN). Although its precise molecular functions are still under debate, FXN is claimed to be primarily involved in the biogenesis of Fe–S clusters, key redox cofactors required for the enzymatic activity of several proteins included the respiratory complexes I, II and III. Interestingly, FXN was observed to be associated to mitochondrial cristae, suggesting a possible functional interaction of the protein with the OXPHOS system. Based on this evidence and on the respiratory defects characterizing FRDA cells, the bacterial frataxin-like protein Nqo15 raised novel questions, since it was identified in the crystal structure of Thermus thermophilus respiratory complex I. Given the extremely similar fold, Nqo15 has been pointed out as a possible, evolutionarily distant frataxin homologue. To explore this hypothesis, a recombinant Nqo15 protein was purified and characterized by means of different spectroscopic techniques, with a particular focus on its iron binding properties, for which FXN has already been extensively characterized. Hopefully, exploring the structure-function correlation of this frataxin-like protein, related to a bacterial respiratory complex I, might provide useful hints about the still elusive functions of FXN.