Yeast iron metabolism

The budding yeast Saccharomyces cerevisiae is an extremely attractive eukaryotic model system for the study of genes involved in iron metabolism. This is because of its short generation time, the ease with which relatively large amounts of... 

In the absence of a demonstrable yeast iron-storage protein (ferritin), we have to recognize that, despite our substantial advances in understanding iron uptake in yeast, we know practically nothing about intracellular iron metabolism - except that is for iron transport into, and out of, mitochondria. 

Fig. 1. Schematic overview of copper trafficking and homeostasis inside the yeast cell. The actions of Mad and Ace 1, copper-dependent metalloregulatory transcription factors, control the production of copper import [copper transporter (Ctr) and reductase (Fre)] and detoxification/sequestration [metallothionein (MT)] machineries, respectively. Three chaperone-mediated delivery pathways are shown. Atxl shuttles Cu(I) to the secretory pathway P-type ATPase Ccc2 (right). CCS delivers Cu(I) to the cytoplasmic enzyme copper-zinc superoxide dismutase (SOD) (left). Coxl7 shuttles Cu(I) to cytochrome c oxidase (CCO) in the mitochondria (bottom). Mitochondrial proteins Scol and Sco2 may also play a role in copper delivery to the CuA and CuB sites of CCO. Copper metabolism and iron metabolism are linked through the actions of Fet3, a copper-containing ferroxidase required to bring iron into the cell (lower right) (see text).

All fungal genomes archived encode at least one MCO of ca 700 residues that contains a carboxyl-terminal transmembrane domain this is in addition to the laccase(s) that many also produce. Most if not all of these membrane-associated MCOs are ferroxidases, and, hke Cp and Hp, play an essential role in the iron metabolism of these fungi. Three of these were represented in the sequences given in Figure 4 (FetSp, Fet5p and Fiol). Of these proteins, the most thoroughly characterized representative is the FetSp protein from baker s yeast, Saccharomyces cerevisiae. 

Recent reviews on copper homeostasis in E. col and yeast are available. Copper and iron metabolism are often intertwined. For instance, mammalian iron metabohsm depends on the copper protein, ceruloplasmin, a ferroxidase that facilitates iron efflux from cells see Copper Proteins Oxidases) Several important human diseases, including Menkes disease and Wilson s disease, result from mutations in copper transport see Metal-related Diseases of Genetic Origin) ... 

The biochemistry and molecular biology of iron metabolism in yeast... 

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