Chemistry Reference
In-Depth Information
3.
Iron, copper, and zinc transport and storage in fungi
As we saw in Chapter 7, during reductive uptake of iron by Saccharomyces cerevisiae, extracellular ferric complexes
are reduced and the ferrous iron that is released is taken up by the low-affinity divalent metal permease (FET4) or the
high-affinity oxidase
FTR1), which was outlined in Fig. 7.1. Copper participates in the
biogenesis of FET3 in a late Golgi compartment via the copper chaperone CCC2. Iron can also be taken up from ferric
siderophore complexes. Iron is clearly required in substantial amounts for haem and Fe
e
permease system (FET3
e
S biosynthesis, as we
described in Chapter 4. Many proteins which contain haem and Fe/S are located in the mitochondria, making the
e
FIGURE 8.14
A model for the mechanism of Fe/S protein biogenesis in mitochondria.
(From
Lill et al., 2006
.
Copyright 2006 With
permission from Elsevier.)
across themitochondrial inner membrane in amembrane potential-dependent manner facilitated by themitochondrial
carrier proteins MRS3 and MRS4, together with other unknown proteins (X). It is then used for haem synthesis from
protoporphyrin IX (PPIX) by ferrochelatase (Hem15) and for the biogenesis of Fe/S proteins. The latter process starts
with the release of sulfur from cysteine by the Nfs1/Isd11 cysteine desulfurase complex and the formation of
a transient Fe/S cluster on the Isu1/2 scaffold proteins. The electron (e
) transfer chain NADH
/
ferredoxin reductase
Arh1
ferredoxinYah1 and the putative iron donor Yfh1 (frataxin) are needed for transient Fe/S cluster synthesis on
Isu1/2. YFH1 may also serve a similar chaperone function in the terminal step of haem biosynthesis supplying iron to
ferrochelatase. The structure of frataxin and its role in the human neurological disease, Friedreich's ataxia, are dis-
cussed in Chapter 21. Yeast strains with a deletion in gene YFH1 accumulate excess iron in the mitochondria, and
undergo mitochondrial oxidative damage. To date, no ferritin-like iron storage protein, like those found in bacteria,
plants, animals, and almost every other living organism, has been reported in asco- and basidiomycetes. Indeed,
scrutiny of the Scerevisiaegenome reveals no protein with convincing homology to consensus sequences for ferritins.
Intracellular iron is stored in the vacuole, which in yeast is a dynamic storage depot associated with the handling in
addition to Fe, of Cu, Zn, Mn, Mg, and Ca. Iron can be mobilised by a similar reductive mechanism to that used in the
high-affinity uptake pathway at the plasmamembrane, involving homologous proteins
/
the reductase, FRE6, and the
e
oxidase/permease, FET5, and FTH1(?)
