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One major source of reactive oxygen species (ROS) is the Fenton reaction: Fe
2+
+ H
2
O
2
Fe
3
+ HO
-
+ HO
�
Mass action implies that ROS generated by the Fenton reaction depend on the intracellular concentration of ferrous ions ([Fe
2+
]) although other metabolic fluxes make it difficult to capture this concentration dependence. Other metals such as Cu
+
may participate in a Fenton reaction and others may even have antioxidant activity; but, until recently, it was also difficult to affect intracellular [Fe
2+
] or the intracellular concentration of other divalent metals by experimental manipulation. This chapter reviews the discovery of a transporter that is involved in Fe
2+
flux and potentially in the flux of other divalent metals and describes some ways to manipulate expression of this transporter.