Iron speciation in the cytosol: an overview

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• The cytosolic iron pool's nature and ligands are poorly understood.
• Candidate ligands and chaperones for cytosolic iron have been proposed.
• Iron's redox activity is influenced by various ligands.

Purpose of the Study:

• To analyze cytosolic non-heme and non-iron-sulfur cluster protein iron-binding sites.
• To investigate the influence of ligands on iron's redox activity.
• To propose a model for the labile cytosolic iron pool.

Main Methods:

• Literature review and analysis of existing data on iron-binding sites.
• Examination of ligand effects on iron redox states.
• Conceptual modeling of iron trafficking pathways.

Main Results:

• Iron(II) glutathione (Fe(II)GS) is identified as the likely labile cytosolic iron pool.
• Fe(II)GS facilitates iron selection over manganese for enzyme incorporation.
• Glutathione and glutaredoxins are critical for iron-sulfur cluster synthesis.

Conclusions:

• Glutathione's role in intracellular iron trafficking is likely universal.
• Fe(II)GS serves as a suitable iron donor for iron-sulfur cluster biosynthesis.
• This finding impacts understanding of iron metabolism in most organisms.