Iron overload impact on P-ATPases

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 Ca²⁺-ATPase. On the Fe²⁺-ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe²⁺ and playing a protection role for the cell. On the Ca²⁺-ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca²⁺ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca²⁺ 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 Ca²⁺-ATPase, and the Fe²⁺-ATPase.