Metabolic response to iron deficiency in Saccharomyces cerevisiae.
Iron is an essential cofactor for enzymes involved in numerous cellular processes, yet little is known about the impact of iron deficiency on cellular metabolism or iron proteins. Previous studies have focused on changes in transcript and proteins levels in iron-deficient cells, yet these changes may not reflect changes in transport activity or flux through a metabolic pathway. We analyzed the metabolomes and transcriptomes of yeast grown in iron-rich and iron-poor media to determine which biosynthetic processes are altered when iron availability falls. Iron deficiency led to changes in glucose metabolism, amino acid biosynthesis, and lipid biosynthesis that were due to deficiencies in specific iron-dependent enzymes. Iron-sulfur proteins exhibited loss of iron cofactors, yet amino acid synthesis was maintained. Ergosterol and sphingolipid biosynthetic pathways had blocks at points where heme and diiron enzymes function, whereas Ole1, the essential fatty acid desaturase, was resistant to iron depletion. Iron-deficient cells exhibited depletion of most iron enzyme activities, but loss of activity during iron deficiency did not consistently disrupt metabolism. Amino acid homeostasis was robust, but iron deficiency impaired lipid synthesis, altering the properties and functions of cellular membranes.
Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Minoo
M
Shakoury-Elizeh
Olga
O
Protchenko
Alvin
A
Berger
James
J
Cox
Kenneth
K
Gable
Teresa M
TM
Dunn
William A
WA
Prinz
Martin
M
Bard
Caroline C
CC
Philpott
D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D047468:Immunoprecipitation; D000090463:Iron Deficiencies; D055432:Metabolomics; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D029701:Saccharomyces cerevisiae Proteins