Non-transferrin-bound iron transporters.

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Cells primarily obtain iron through transferrin receptor-mediated endocytosis.
• Iron overload conditions lead to non-transferrin-bound iron (NTBI), a toxic form of iron.
• NTBI accumulation contributes to tissue damage in diseases like hemochromatosis.

Purpose of the Study:

• To review the uptake mechanisms of NTBI across various tissues and cells.
• To summarize the evidence for and against specific transporters involved in NTBI uptake.
• To highlight the role of NTBI in iron homeostasis and overload pathology.

Main Methods:

• Literature review of studies on iron transport and NTBI.
• Analysis of evidence for various NTBI transporters, including ZIP14, calcium channels, DMT1, ZIP8, and TRPC6.
• Synthesis of findings on NTBI uptake in different organs and cell types.

Main Results:

• NTBI is a toxic iron species found in plasma during iron overload.
• NTBI is a normal constituent of brain interstitial fluid, supplying iron to CNS cells.
• Multiple transporters, including ZIP14, calcium channels, DMT1, ZIP8, and TRPC6, are implicated in NTBI uptake.

Conclusions:

• NTBI plays a significant role in tissue iron overload and associated pathologies.
• Understanding NTBI transporters is critical for managing iron overload disorders.
• Further research is needed to elucidate the precise roles of individual transporters in NTBI uptake.