Glutathione-coordinated metal complexes as substrates for cellular transporters

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Biology

Background:

• Glutathione (GSH) is a crucial thiol-containing molecule in all cells.
• It plays vital roles in detoxification, including metal sequestration, reduction, and efflux.
• ATP-binding cassette (ABC) transporters like MRP1 and MRP2 facilitate metal detoxification by exporting metal-glutathione complexes.

Purpose of the Study:

• To trace the evolutionary path of metal efflux transporters.
• To elucidate the function of the mammalian ABCB7 transporter.
• To understand the role of ABCB7 in iron-sulfur cluster transport.

Main Methods:

• Comparative analysis of bacterial and mammalian transporter proteins.
• Bioinformatic analysis of protein evolution.
• Mitochondrial localization studies of ABCB7.

Main Results:

• The bacterial Atm1 protein, involved in metal-glutathione efflux, is an evolutionary precursor to mammalian ABCB7.
• ABCB7 is localized to the inner mitochondrial membrane in mammals.
• ABCB7 facilitates the transport of iron-sulfur clusters coordinated with glutathione from mitochondria to the cytosol.

Conclusions:

• The function of the Atm1/ABCB7 transporter family has shifted from general cellular metal detoxification to a specialized role in iron-sulfur cluster metabolism.
• ABCB7's mitochondrial localization highlights its critical role in cellular iron homeostasis and the biogenesis of iron-sulfur proteins.