TABLE 5.

Changes in expression of genes involved in iron homeostasis in lactate-challenged chemostat cultures compared to reference anaerobic chemostat cultures^a

Gene(s)	Descriptionb	Fold change at:
		pH 3	pH 5
AFT1/RCS1	Transcription factor involved in iron utilization and homeostasis; activates the expression of target genes in response to changes in iron availability	1.0	3.3
AFT2	Iron-regulated transcriptional activator, required for iron homeostasis and resistance to oxidative stress	1.0	1.6
ARN1	Transporters that specifically recognize siderophore-iron chelates	2.3	34
ARN3/SIT1	Transporters that specifically recognize siderophore-iron chelates; transcription is induced during iron deprivation and diauxic shift	1.0	11
ARN4/ENB1	Endosomal ferric enterobactin transporter, expressed under conditions of iron deprivation; member of the major facilitator superfamily; expression is regulated by Rcs1p	1.8	4
ATX1	Cytosolic copper metallochaperone that transport copper to the secretory vesicle copper transporter Ccc2p for eventual insertion into Fet3p	1.9	4
CCC2	Cu2+-transporting P-type ATPase, required for export of copper from the cytosol into an extracytosolic compartment	2.0	7
CTH1	Member of the CCCH zinc finger family; may function with Tis11p in iron homeostasis	1.0	2.1
CTR1	High-affinity copper transporter of the plasma membrane; mediates nearly all copper uptake under low-copper conditions; transcriptionally induced at low-copper levels and degraded at high-copper levels	−2.2	−2.7
FET3	Ferro-O2-oxidoreductase required for high-affinity iron uptake and involved in mediating resistance to copper ion toxicity; belongs to the class of integral membrane multicopper oxidases	7.4	103
FET4	Low-affinity Fe(II) transporter of the plasma membrane	1.3	−20
FIT1	Mannoprotein that is incorporated into the cell wall via a glycosylphosphatidylinositol (GPI) anchor; involved in the retention of siderophore-iron in the cell wall	1.5	8
FIT2	Mannoprotein that is incorporated into the cell wall via a GPI anchor; involved in the retention of siderophore-iron in the cell wall	1.9	60
FIT3	Mannoprotein that is incorporated into the cell wall via a GPI anchor; involved in the retention of siderophore-iron in the cell wall	3.1	57
FRE1	Ferric reductase and cupric reductase; reduces siderophore-bound iron and oxidized copper prior to uptake by transporters; expression induced by low copper and iron levels	−1.5	1.3
FRE2	Ferric reductase and cupric reductase; reduces siderophore-bound iron and oxidized copper prior to uptake by transporters; expression induced by low copper and iron levels	1.5	32
FRE3	Ferric reductase, reduces siderophore-bound iron prior to uptake by transporters; expression induced by low iron levels	1.0	9
FRE5	Putative ferric reductase with similarity to Fre2p; expression induced by low iron levels	1.0	3
FRE6	Putative ferric reductase with similarity to Fre2p; expression induced by low iron levels	1.0	3
FTR1	High affinity iron permease involved in the transport of iron across the plasma membrane; forms complex with Fet3p; expression is regulated by iron	2.2	1.7
HMX1	Endoplasmic reticulum-localized, heme-binding peroxidase involved in the degradation of heme; does not exhibit heme oxygenase activity despite similarity to heme oxygenases; expression regulated by Aft1p	1.5	6
ISU1	Conserved protein of the mitochondrial matrix; performs a scaffolding function during assembly of iron-sulfur clusters; interacts physically and functionally with yeast frataxin (Yfh1p)	1.0	2.1
ISU2	Conserved protein of the mitochondrial matrix, required for synthesis of mitochondrial and cytosolic iron-sulfur proteins, performs a scaffolding function in mitochondria during Fe/S cluster assembly	2.1	2.3
MRS4	Mitochondrial iron transporter of the mitochondrial carrier family (MCF), very similar to and functionally redundant with Mrs3p; functions under low-iron conditions; may transport other cations in addition to iron	1.0	2.4
SMF3	Putative divalent metal ion transporter involved in iron homeostasis; transcriptionally regulated by metal ions; member of the Nramp family of metal transport proteins	1.6	2.2
TIS11	mRNA-binding protein expressed during iron starvation; binds to a sequence element in the 3′ untranslated regions of specific mRNAs to mediate their degradation; involved in iron homeostasis	4.1	45
YBR047W	Mitochondrial protein of unknown function; contains Rcs1p and Aft2p binding domains (58)	1.0	19
YHL035C	Putative vacuolar multidrug resistance protein; contains Rcs1p and Aft2p binding domains (58)	1.0	27

^aRelative transcript levels of genes involved in iron homeostasis in lactate-challenged and reference anaerobic chemostat cultures of S. cerevisiae CEN.PK 113-7D at pH 3 and pH 5. Fold change is relative to that of reference anaerobic chemostat cultures (with no lactic acid added) at the corresponding pH.

^bGene descriptions originate from the Saccharomyces Genome Database (www.yeastgenome.org) and from the references noted.