The importance of ferric reductases for iron uptake in humans

Iron is an important metal for all living organisms because it functions as a critical redox catalyst for essential life processes. In the human body, iron is associated with various proteins that regulate vital functions, such as DNA synthesis, oxygen transport and storage, and energy production. Both iron deficiency and excess can negatively affect cellular function. Insufficient iron impairs cell activity, whereas excess iron, particularly in its ferrous (Fe 2+ ) form, can generate harmful reactive oxygen species through the Fenton reaction. Consequently, the body tightly controls the oxidation state and distribution of iron using specialized proteins. Under physiological conditions, iron mainly exists as ferric (Fe 3+ ) compounds like Fe(OH) 3 , which are poorly soluble and difficult for organisms to use. To overcome this, living systems have evolved mechanisms to efficiently acquire iron from their environment. A key strategy involves reducing Fe 3+ to the more soluble Fe 2+ , which can then be transported across cell membranes by specific metal transporters. This reduction is often mediated by heme-containing enzymes that facilitate electron transfer. This review focuses on the characteristics of ferric reductases that participate in iron acquisition in humans, highlighting recent advances in research.