Cellular iron metabolism

In 1976, Hamish Munro proposed a model for the translational control of ferritin synthesis (Zahringer et al., 1976), which not only represents a crucial and remarkably far-sighted contribution to our understanding of cellular iron metabolism, but also in the more general context of the posttranscriptional control of gene expression. 

Klausner, R.D., Roualt, T. and Harford,J. B. Regulating the fate of mRNA the control of cellular iron metabolism (1993) Cell 72,19-28... 

The regulation of cellular iron homeostasis is to a large degree controlled at the level of the translation of the mRNAs of proteins involved in cellular iron metabolism (Rouault, 2006 Wallander et al., 2006). The key players in this post-transcriptional regulation are two iron regulatory proteins (IRPl and 1RP2), which function as... 

The essentiality of copper arises from its specific incorporation into a large number of enzymatic and structural proteins. The role of copper in oxidation-reduction enzyme activities is the consequence of its ability to function as an electron transfer intermediate. Thus, copper is present in enzymes involved in cellular respiration, free radical defense, neurotransmitter function, connective tissue biosynthesis, and cellular iron metabolism. 

Figure 8.3 Regulation of cellular iron metabolism by the IRE/IRP system. Iron supplementation increases the iron supply and inactivates binding of IRPs to IREs, resulting in degradation of TfR mRNA and translation of the mRNAs of H- and L-ferritin. These responses lead to deereased iron uptake and elevated iron storage. Conversely, iron depletion activates binding of IRPs to IREs, resulting in stabilization of TfR mRNA and translational inhibition of the mRNAs of H- and L-ferritin. These responses lead to increased iron uptake and reduced iron storage.

Klausner, R., Rouault, TA., Haiford, JB., Regulating the fate of mRNA The control of cellular iron metabolism. Cell, 1993. 72 p. 19-28. 

Intracellular Iron Metabolism and Cellular Iron Homeostasis... 

While unicellular fungi do not require metal transport systems, multi-cellular fungi and plants most certainly do, and we consider their transport in plants, and then consider how metal ions are sequestered in storage compartments before addressing their homeostasis. Once again, we consider in turn these processes for iron, copper and zinc. Since iron metabolism has been most intensively studied in S. cerevisiae, of all the fungi, we will focus our attention on iron homeostatic mechanisms, however, as the reader will see shortly, copper and zinc homeostasis have many similarities. 

An inevitable consequence of ageing is an elevation of brain iron in specific brain regions, e.g. in the putamen, motor cortex, pre-frontal cortex, sensory cortex and thalamus, localized within H- and L-ferritin and neuromelanin with no apparent adverse effect. However, ill-placed excessive amounts of iron in specific brain cellular constituents, such as mitochondria or in specific regions brain, e.g. in the substantia nigra and lateral globus pallidus, will lead to neurodegenerative diseases (Friedreich s ataxia and Parkinson s disease (PD), respectively). We discuss here a few of the examples of the involvement of iron in neurodegenerative diseases. From more on iron metabolism see Crichton, 2001. 

Lill R, Muhlenhoff U (2006) Iron-sulfur protein biogenesis in eukaryotes components and mechanisms. Annu Rev Cell Dev Biol 22 457-486 Lill R, Diekert K, Kaut A, Lange H, Pelzer W, Prohl C, Kispal G (1999) The essential role of mitochondria in the biogenesis of cellular iron-sulfur proteins. Biol Chem 380 1157-1166 Lindmark DG (1980) Energy metabolism of the anaerobic protozoon Giardia lamblia. Mol Biochem Parasitol 1 1-12... 

---