The fission yeast ferric reductase gene frp1+ is required for ferric iron uptake and encodes a protein that is homologous to the gp91-phox subunit of the human NADPH phagocyte oxidoreductase.

Abstract

We have identified a cell surface ferric reductase activity in the fission yeast Schizosaccharomyces pombe. A mutant strain deficient in this activity was also deficient in ferric iron uptake, while ferrous iron uptake was not impaired. Therefore, reduction is a required step in cellular ferric iron acquisition. We have clonedfrpl1, the wild-type allele of the mutant gene.frpl + mRNA levels were repressed by iron addition to the growth medium. Fusion of 138 nucleotides of frpl + promoter sequences to a reporter gene, the bacterial chloramphenicol acetyltransferase gene, conferred iron-dependent regulation upon the latter when introduced into S. pombe. The predicted amino acid sequence of the frp1+ gene exhibits hydrophobic regions compatible with transmembrane domains. It shows similarity to the Saccharomyces cerevisiae FREI gene product and the gp9l-phox protein, a component of the human NADPH phagocyte oxidoreductase that is deficient in X-linked chronic granulomatous disease.

Iron: Nutritious, Noxious, and Not Readily Available

“…Because the respiratory burst oxidase is involved in the movement of a single electron from NADPH across the PM to molecular oxygen, the similarity to FREl may be significant; the yeast Fe(II1) reductase must move single electrons across the PM as well, although in the case of Fe(II1) reductase, the terminal electron acceptor is Fe(II1). The yeast Fe(II1) reductase and the human granulocyte reductase are most similar in regions of the protein thought to be involved in the binding of flavin adenine dinucleotide and NADPH (Roman et al, 1993). These regions are also conserved with the Schizosaccharomyces pombe Frpl protein.…”

“…These regions are also conserved with the Schizosaccharomyces pombe Frpl protein. The Frpl gene, like the FREl gene of yeast, was identified by complementation of an S. pombe Fe(II1) reductase mutant (Roman et al, 1993). It has been suggested that FRE1, Frpl, and gp91-phox are members of a nove1 family of PM electron transport proteins responsible for mobilizing cytoplasmic reducing equivalents and donating them to extracellular substrates (Roman et al, 1993).…”

“…The Frpl gene, like the FREl gene of yeast, was identified by complementation of an S. pombe Fe(II1) reductase mutant (Roman et al, 1993). It has been suggested that FRE1, Frpl, and gp91-phox are members of a nove1 family of PM electron transport proteins responsible for mobilizing cytoplasmic reducing equivalents and donating them to extracellular substrates (Roman et al, 1993). The degree of amino acid identity between the S. pombe Frpl and the Saccharomyces cerevisiae FREl is quite limited (27% amino acid identity and 49% similarity).…”

Nitrate regulation of Fe reduction and transport by Fe‐limited Thalassiosira oceanica

“…may be relevant. We note that ferric chelate reductases from yeast and Arabidopsis have a high degree of homology with members of the ferredoxin-NADP ϩ reductase family of reductases, which include NR (Roman et al 1993;Segal and Abo 1993;Robinson et al 1999). The ability of NH 4 ϩ -grown T. oceanica to reduce Fe, although at a slower rate, may imply that they too have low levels of a NR-like redox enzyme in the plasmalemma.…”

Partial characterization and identification of a transferrin-like molecule of pathogenic yeast Cryptococcus neoformans.

“…A second alternative mechanism to siderophore-mediated iron uptake has been postulated, involving the extracellular reduction of ferric iron followed by the uptake of the soluble ferrous species (17). The involvement of ferric reductase in cellular iron uptake has also been proposed in soybeans (2), in Saccharomyces cerevisiae (4), and in S. pombe (16). The role of the ferric reductase enzyme in cellular iron uptake in Cryptococcus has not been studied nor is the mechanism by which ferrous iron crosses the membrane and enters yeast cells in general, and C. neoformans in particular, fully understood.…”