Labile iron pool

Cells contain low concentrations of transition-metal ions, notably iron and copper. For example, the DNA scaffolding protein is reported to contain copper (Lewis and Laemmli 1982). However, no intracellular free copper is detectable (Rae et al. 1999). The intracellular labile iron pool is reported to be around mi-... 

Engelmann MD, Bobier RT, Hiatt T, Cheng IF (2003) Variability of the Fenton reaction characteristics of the EDTA, DTPAand citrate complexes of iron. BioMetals 16 519-527 Epsztejn S, Kakhlon O, Glickstein H, Breuer W, Cabantchik I (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 248 31-40 Faraggi M, Hemmerich P, Pecht I (1975) Oj-affinity of flavin radical species as studied by pulse radiolysis. FEBS Lett 51 47-51... 

When all the Fe2+ is consumed (the intracellular labile iron pool is around micromolar Epsztejn et al. 1997), the reaction should come to a standstill. In the cellular systems that have been investigated, this seems not to be the case, and it has been postulated that Fe3+ (possibly complexed to DNA) is reduced by H202 in a slow reaction [reaction (49) Ward et al. 1985],... 

The majority of body iron is not chelatable (iron from cytochromes and hemoglobin). There are two major pools of chelatable iron by DFO (19). The first is that delivered from the breakdown of red cells by macrophages. DFO competes with transferrin for iron released from macrophages. DFO will also compete with other plasma proteins for this iron, when transferrin becomes saturated in iron overload. The quantity of chelatable iron from this turnover is 20mg/day in healthy individuals and iron chelated from this pool is excreted in the urine (19). The second major pool of iron available to DFO is derived from the breakdown of ferritin and hemosiderin. The ferritin is catabolized every 72 hours in hepatocytes, predominantly within lysosomes (I). DFO can chelate iron that remains within lysosomes shortly after ferritin catabolism or once this iron reaches a dynamic, transiently chelatable, cytosolic low-molecular-weight iron pool (20). Cellular iron status, the rate of uptake of exogenous iron, and the rate of ferritin catabolism are influent on the level of a labile iron pool (21). Excess ferritin and... 

In most cases, the reversal of symptomatic myocardiopathy has been achieved without drug toxicity (19,43). Davis and Porter (19) and Tsironi et al. (44) confirmed clinically the laboratory data of Link et al. (45) that DFO therapy reverses cardiac arrhythmias in some patients previously unresponsive to medical treatment. This may be attributed to removal of a toxic labile iron pool. They also mentioned improvement of left ventricular ejection fraction in seven of nine patients. It is important to note that oral chelators are less effective than DFO and are unable to prevent cardiac mortality in patients with established heart disease (46). 

Konijn AM, Glickstein H, Vaisman B, et al, The cellular labile iron pool and intracellular ferritin in K562 cells. Blood 1999 94 2128-2134. 

Epsztejn S, Kakhlon O, Glickstein H, etal, Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 1997 248 3 I —40. 

Picard, V. Epsztejn, S. Santambrogio, P. Cabantchik, Z. 1. Beaumont, C. Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells. J. Biol. Chem. 273 15382-15386 1998. 

Kakhlon O, Cabantchik Zl. The labile iron pool characterization, measurement, and participation in ceEu-lar processes. Free Radic Biol Med 2002 33 1037-46. 

While most soluble cellular iron is associated with an ill-defined labile iron pool, much of the iron that is used by the cell is found in the form of specific iron cofactors especially as iron-sulfur clusters and hemes. The biosynthesis of iron-sulfur centers has only come of age within the past decade following the characterization of operons encoding cluster assembly genes by Dean and coworkers 4), In eukaryotes, homologous proteins are nuclear transcribed. While predominantly localized within the mitochondrial matrix, one group has reported cytosolic ISU (cluster assembly protein) and NFS (S-donor protein) in human cell lines (5). Alternative cytoplasmic cluster maturation proteins have also been proposed (6). Whether the cytosolic components represent an independent assembly apparatus is unclear, nevertheless, both models support a role for ISU-mediated assembly of [2Fe-2S] building blocks prior to delivery to a target protein (7-P). 

Kl. Kakhlon, O., and Cabantchik, Z. I., The labile iron pool Characterization, measurement, and participation in cellular processes. Free Radio. Biol. Med. 33, 1037-1046 (2002). 

The labile iron pool has recently been defined by Cabantchik et al. [103] as the pool of iron labilly bound to low-molecular complexes available for redox reactions. Typical LIP concentration in the cell does not exceed 1 pM [104]. 

Kumar, R. (1979) Mechanism of anemia of chronic infection-estimation of labile iron pool and interpretation of ferrokinetic data. Ind. J. Med. Res. 70 455-462. 

It is well eharaeterized that iron acquisition and storage are co-ordinately regulated by iron at the post-transcriptional level. mRNAs encoding TfRl and ferritin (H and L ehains) contain iron-responsive elements (IREs) in their untranslated regions (UTRs). The size of the labile iron pool (LIP) modulates... 

Tenopoulou, M. Kurz, T. Doulias, R. T. Galaris, D. Brunk, U. T. Does the calcein-AM method assay the total cellular labile iron pool or only a fraction of it Biochem. J. 2007, 403, 261-266. 

Pinero, D.J., et al.. Interleukin-1 beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool [In Process Citation]. Biochim Biophys Acta, 2000.1497(3) p. 279-88. 

---