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One essential nutrient is iron, which nearly all organisms require as a cofactor in metalloproteins that carry out essential cellular functions (e.g., DNA replication).
Iron inside cells is important for many processes like making DNA and helping mitochondria work. However, it can also cause a type of cell death called ferroptosis, which happens when certain reactive oxygen species (ROS) are involved. Lysosomes, known for breaking down and recycling materials, play a key role in managing iron levels in cells. They also help connect signals related to metabolism and cell death from different parts of the cell.
Mammalian cells and most of the bacteria in the gut microbiota rely on iron for many cellular processes
A 70-kg adult human has about 5 g of iron (about 10H-3 M for body volume), whereas a bacterial cell of 10H-9 /cm3 requires 10H5 to 10H6 ferric ions per generation to maintain the required 10 H6 M internal concentration.
Human iron metabolism is remarkably efficient, as only 0.5–1 mg of the approximately 4–5 g of total body iron in adults is lost daily.
The human serum iron transport protein, transferrin, maintains the free ferric ion concentration at about 10H-24 M.
Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication.
However, the redox potential of iron also contributes to its toxicity; thus, iron concentration and distribution must be carefully controlled.
The redox potential of iron also generates cellular toxicity under conditions of iron overload. Reactive oxygen intermediates are generated during the course of normal cellular homeostasis. In the presence of such reactive oxygen species, iron can catalyze the Fenton reaction to generate hydroxyl radicals that damage lipids, DNA, and protein.
Prior to transport into duodenal enterocytes, dietary ferric iron is reduced by ferric reductases present in the apical brush border.
Ferrous iron is transported into the cell by DMT1, after which it can be used for cellular processes, stored in ferritin, or exit the cell via ferroportin (FPN).
Iron Is sequestered by high-affinity chelators such as Transferrin, Hemoglobin, and Ferritin
During episodes of gut inflammation, mucosal epithelial cells and immune cells restrict bacterial proliferation by producing iron-scavenging proteins, such as lactoferrin.
B. thetaiotaomicron secretes a lipoprotein onto the cell surface and into the extracellular milieu to acquire xenosiderophores.
Siderophores bound to this protein are shielded from lipocalin-2-mediated sequestration but are readily utilized by S. Tm. By recapturing siderophores from commensal bacteria, S. Tm can recover a pool of siderophores that are otherwise sequestered by host proteins.
Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication.