[The protein degradation system involved in the regulation of iron metabolism]

Iron is an essential nutrient for almost all organisms, but at the same time excess iron is toxic to generate radicals and damages important macromolecules. Thus, organisms have developed a strict regulatory system for iron metabolism. We have studied the iron-mediated regulatory mechanism of a regulator of the iron metabolism, IRP2, and found that IRP2 is regulated by an oxidation-induced degradation, which is triggered by heme and molecular oxygen. Recent advances in the analyses of iron regulation in cells and animals reveal that the protein degradation system is involved in the iron-mediated regulation of another regulator of iron metabolism, IRP1. Considering that heme is generated in the matrix of mitochondria, our observation that IRP2 is regulated by the protein degradation pathway triggered by the heme-mediated oxidation indicates the involvement and importance of mitochondria in cellular iron sensing as well as the regulation of the iron metabolism.