Mitochondrial ferritin: a new player in iron metabolism.
Mitochondrial ferritin (MtF) is a novel H-type ferritin encoded by an intronless gene on chromosome 5q23.1. The protein is synthesized as a precursor of about 30 kDa that is targeted to mitochondria by a leader sequence of 60 amino acids. This leader is proteolytically removed inside the mitochondria and the resulting 22 kDa subunit forms typical ferritin shells. These shells have ferroxidase activity and are therefore likely to sequester potentially harmful free iron. However, this may be a limited function since MtF has a very restricted tissue expression. High amounts are found in testis but only very low levels are found in iron storage organs. The levels of MtF appear to correlate more with mitochondrial abundance than with iron metabolism. MtF does not seem to be an obligatory intermediate in transfer of free iron to heme and other iron compounds in mitochondria. However, its level increases dramatically in sideroblastic anemia when heme synthesis is disrupted. This increased synthesis does not appear to involve the classical translational control since MtF mRNA lacks an apparent iron response element. In transfected HeLa cells added iron is incorporated as quickly into MtF as into cytosolic ferritin. In addition, increased levels of MtF cause a redistribution of iron from cytosol to mitochondria and this effect is enhanced by iron chelation. Thus high levels of MtF result in an iron deficient phenotype in cytosol with decreased expression of ferritin and increased expression of transferrin receptor. This avidity for iron may explain why MtF levels are maintained at low levels in most normal cells. The regulation of MtF expression and possible therapeutic applications of MtF in neurological disorders involving increased iron deposition are topics for future research.
Drysdale
Jim
J
Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. jim.drysdale@tufts.edu
Arosio
Paolo
P
Invernizzi
Rosangela
R
Cazzola
Mario
M
Volz
Armin
A
Corsi
Barbara
B
Biasiotto
Giorgio
G
Levi
Sonia
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004900:Erythroblasts / Q000378:metabolism; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
D005293:Ferritins; D007501:Iron