To test the effect of iron deficiency on mtDNA in the absence of lysosomal perturbations, we used fibroblasts obtained from mice lacking the iron regulatory proteins IRP1 and IRP2, in which the expression of heavy and light ferritin chains is robustly up-regulated, and for that reason are functionally iron deficient (all available iron is stored in the ferritin oligomers, and thus biologically inactive) (Meyron-Holtz et al., 2004). Here, ACO1 is linked to Iron deficiency anemia.