A human mitochondrial ferritin encoded by an intronless gene

Ferritin is a ubiquitous protein that plays a critical role in regulating i ntracellular iron homoeostasis by storing iron inside its multimeric shell. It also plays an important role in detoxifying potentially harmful free fe rrous iron to the less soluble ferric iron by virtue of the ferroxidase act ivity of the H subunit. Although excess iron is stored primarily in cytopla sm, most of the metabolically active iron in cells is processed in mitochon dria. Little is yet known of how these organelles regulate iron homeostasis and toxicity. Here we report an unusual intronless gene on chromosome 5q23 .1 that encodes a 242-amino acid precursor of a ferritin II-like protein. T his 30-kDa protein is targeted to mitochondria and processed to a 22-kDa su bunit that assembles into typical ferritin shells and has ferroxidase activ ity. Immunohistochemical analysis showed that it accumulates in high amount s in iron-loaded mitochondria of erythroblasts of subjects with impaired he me synthesis. This new ferritin may play an important role in the regulatio n of mitochondrial iron homeostasis and heme synthesis.