Fig. 8.

Working model to explain the protective effect of NO in Yfh1-deficient cells. A, Yfh1 contributes to maintain mitochondrial iron in a reduced and/or safe form. Fe-containing proteins (notably Fe-S proteins) retain Aft1 in the cytosol. B, loss of Yfh1 leads to increased presence of anomalous iron species which trigger a mild activation of Aft1 trough unknown mechanisms. A moderate increase in iron uptake proteins can be found. C, a vicious cycle takes place: the more iron enters the cell, the more anomalous iron species are formed and Aft1 is activated more strongly. Furthermore, Cth2 is expressed, leads to decreased expression of Fe-containing proteins and the repressing effect of these Fe-proteins on Aft1 is lost. A high increase in iron uptake proteins can be detected. D, In the absence of Yhb1, NO levels increase and NO can form iron-nitrosyl complexes which can prevent the formation of anomalous iron species.