Friedreich Ataxia (FA) is a rare genetic cardio-neurodegenerative disease caused by mutations in the FXN gene resulting in low levels of frataxin, a mitochondrial protein. While most patients are homozygous for a GAA triplet expansion in the first intron of the FXN gene, 5% are compound heterozygous for a GAA expansion in one allele and a point mutation in the other allele. It is well-established that frataxin-deficient mammals present deregulated iron homeostasis, mitochondrial dysfunction and increased oxidative stress. Nevertheless, the tissue-specificity of these alterations has not been analysed in detail due to the lack of suitable animal models. Our lab has recently developed a new FA mouse model based on the human pathological point mutation I154F. It presents low frataxin content in all the tissues and neurobehavioral defects resembling FA patients. Therefore, it is the first model which allows the study of the systemic consequences of frataxin deficiency on iron homeostasis. In this regard, we have observed an increase in total iron content in the nervous system and the liver of FXNI151F mice. Moreover, Iron Regulatory Protein 1 (IRP1) content is decreased in these tissues, while heart presents normal iron and IRP1 levels, and increased IRP2 content. Remarkably, in the liver, IRP1 decrease precedes iron accumulation and iron-sulfur loss. We conclude that frataxin deficiency causes tissue-specific alterations in iron homeostasis. In the liver, reduction of IRP1 content may disturb iron sensing and affect the control of systemic iron metabolism, contributing to anomalous iron distribution among tissues.