Disease relevance of FTMT

• In contrast, many erythroblasts from patients with sideroblastic anemia (82%-90% in XLSA and 36%-84% in RARS) were positive for MtF, which regularly appeared as granules ringing the nucleus [1].
• Erythroid cells from 13 patients with refractory anemia with ring sideroblasts (RARS) and 3 patients with X-linked sideroblastic anemia (XLSA) were analyzed for the distribution of cytoplasmic H ferritin (HF) and MtF using immunocytochemical methods [1].
• Furthermore, MtF expression prevented the development of mitochondrial iron overload, preserved mitochondrial DNA integrity and increased cell resistance to H2O2 [2].
• We analyzed cytochrome c release, MtF expression, and gene expression during erythroid differentiation in bone marrow cells from myelodysplastic syndrome (MDS) patients and healthy controls [3].
• OBJECTIVE: To estimate HIV incidence among male-to-female transgendered persons (MtF transgendered persons) who repeatedly tested for HIV antibodies at public San Francisco counseling and testing sites between July 1997 and June 2000 [4].

High impact information on FTMT

• The proportion of RARS erythroblasts that were MtF+ increased further upon in vitro maturation [3].
• The human MtF precursor was efficiently imported by yeast mitochondria and processed to functional ferritin that actively sequestered iron in the organelle [2].
• MtF expression in human and mouse is restricted to the testis and few tissues, and it is abundant in the erythroblasts of patients with sideroblastic anemia, where it is thought to protect the mitochondria from the damage caused by iron loading [2].
• Reverse transcription-polymerase chain reaction studies demonstrated the presence of MtF mRNA in circulating reticulocytes of 2 patients with XLSA but not in controls [1].
• Neither effect occurred with the mutant MtF with the inactivated ferroxidase center [5].

Biological context of FTMT

• Our results indicate that exogenous iron is as available to mitochondrial ferritin as it is to cytosolic ferritins and that the level of MtF expression may have profound consequences for cellular iron homeostasis [5].
• Mitochondrial ferritin (MtF) is a newly identified ferritin encoded by an intronless gene on chromosome 5q23 [5].
• Increased levels of MtF both in transient and in stable transfectants resulted in a greater retention of iron as MtF in mitochondria, a decrease in the levels of cytosolic ferritins, and up-regulation of transferrin receptor [5].
• MtF exhibits sigmoidal kinetics of mineralization more characteristic of an L-chain than an H-chain ferritin [6].
• The recently discovered human mitochondrial ferritin (MtF), unlike other mammalian ferritins, is a homopolymer of 24 subunits that has a high degree of sequence homology with human H-chain ferritin (HuHF) [6].

Anatomical context of FTMT

• There was a highly significant relationship between the percentage of MtF(+) erythroblasts and that of ring sideroblasts (Spearman R = 0.90; P <.0001) [1].
• These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia [1].

Associations of FTMT with chemical compounds

• Mature MtF was found in the matrix of mitochondria, where it is a homopolymer [5].
• Stopped-flow absorption spectrometry of Fe(II) oxidation by O(2) in MtF shows the formation of a transient diiron(III) mu-peroxo species (lambda(max) = 650 nm) as observed in HuHF [6].
• However, the 2Fe(II) + H(2)O(2) detoxification reaction found in HuHF does not occur in MtF [6].
• Also, as for HuHF, minimal hydroxyl radical is produced during the oxidative deposition of iron in MtF using O(2) as the oxidant [6].
• Site-directed mutagenesis reveals that serine 144, a residue situated near the ferroxidase center in MtF but absent from HuHF, is one player in this impairment of activity [6].

Other interactions of FTMT

• 1. The mature recombinant MtF has a ferroxidase center and binds iron in vitro similarly to H-ferritin [5].

References