REVIEW ARTICLE Iron overload impact on P-ATPases Leilismara Sousa 1 & Marco Tulio C. Pessoa 1 & Tamara G. F. Costa 1 & Vanessa F. Cortes 1 & Herica L. Santos 1 & Leandro Augusto Barbosa 1 Received: 21 March 2017 /Accepted: 23 December 2017 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na + ,K + -ATPase and the Ca 2+ -ATPase. On the Fe 2+ -ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe 2+ and playing a protection role for the cell. On the Ca 2+ -ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca 2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca 2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na + ,K + -ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na + ,K + - ATPase, the Ca 2+ -ATPase, and the Fe 2+ -ATPase. Keywords Iron overload . Oxidative stress . Na + ,K + -ATPase . Ca 2+ -ATPase . Fe 2+ -ATPase . P-type ATPase Iron overload Iron is a chemical element that is active in the fundamental physiological processes for human life, such as in oxygen transportation, DNA synthesis, oxidative phosphorylation, and the inactivation of free radicals [1, 2]. An iron overload can be toxic to the body because iron free form can act as an oxidative reaction catalyzer, and consequently, it produces superoxide and hydroxyl free radicals, increasing the protein oxidation/nitration [2–4]. The main complications due to an iron overload occur in the liver and in cardiovascular diseases, diabetes, arthritis, neurodegenerative disorders, and increased infection and thrombosis risk [5–9]. The main and most discussed disease that is related to an iron overload is hered- itary hemochromatosis type 1, which involves mutations in the HFE gene [10]. Besides hereditary hemochromatosis, there are other causes of an iron overload in organisms, such as in the thalassemia, sickle-cell anemia, successive blood transfusions, long-term hemodialysis, aplastic anemia, sideroblastic anemia, alcoholic liver disease, and porphyria cutanea tarda [11, 12]. Although the global prevalence of iron overload is increasing in epidemic proportions, the therapy does not follow the same route and it is currently very limited [13]. P-ATPases The transport and the maintenance of the ionic gradient across the cell membranes are very important in order to guide the main cell processes. It is to be expected that changes in the cell homeostasis could lead to severe physiological consequences. Since the P-ATPases are expressed throughout the whole body, a fully and constant enzyme functioning is needed to keep an order in the main organs, such as in the kidney, in the heart, in the muscles, and in the brain (Fig. 1). * Leandro Augusto Barbosa lbarbosa.ufsj@gmail.com 1 Laboratório de Bioquímica Celular, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João del Rei, Av Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil Annals of Hematology https://doi.org/10.1007/s00277-017-3222-4