Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis

Pazos-Gil, M., Medina-Carbonero, M., Sanz-Alcázar, A., Portillo-Carrasquer,M., Oliveira-Jorge, L., Hernández, G., Sánchez, M., Delaspre, F., Cabiscol, E., Ros, J., Tamarit, J.,Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis, iScience(2026), doi: doi:10.1016/j.isci.2025.11462 

Our results reveal tissue-specific alterations of Iron Regulatory Proteins. In the heart, IRP2 accumulation is observed, likely triggered by iron-sulfur deficiency, while IRP1 is decreased in the cerebellum and liver. We also found elevated iron levels in mutant mice. Accumulation was particularly pronounced in the cerebellum, where increases were already evident at 10 weeks. Hepatic accumulation was not manifested until 21 weeks and was more pronounced in females. Overall, these findings indicate that frataxin deficiency disrupts iron homeostasis in a tissue-, age-, and sex- dependent manner, and provide novel insights into the mechanisms causing these perturbations.