The Cellular Response To Iron Starvation And Intoxication

Philpott, Caroline C.

Abstract

Our microarray analysis unexpectedly revealed that other metabolic pathways are regulated in response to iron availability. The iron-dependent enzyme glutamate synthetase is also transcriptionally down-regulated in response to iron deprivation, and we have characterized the transcriptional control regions of this gene to identify the iron-responsive sequences. To identify the transcription factor that controls the iron-dependent activation of GLT1, we are carrying out screens for genes that stimulate GLT1 expression under conditions of iron deprivation. ? In some yeast species, such as Pichia guillermondii, the biosynthesis of riboflavin is activated in response to iron deficiency. In collaboration with the laboratory of Yuriy Boretsky at the Institute of Cell Biology, NAS, Ukraine, we are developing tools to study gene function in this industrially important yeast, and we have identified a transcription factor that is required for the induction of riboflavin biosynthesis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK054507-10
• Application #: 7593667
• Support Year: 10
• Fiscal Year: 2007
• Total Cost: $251,200

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• Country: United States

Publications

Boretsky, Yuriy R; Pynyaha, Yuriy V; Boretsky, Volodymyr Y et al. (2007) Development of a transformation system for gene knock-out in the flavinogenic yeast Pichia guilliermondii. J Microbiol Methods 70:13-9

Kaplan, Jerry; McVey Ward, Diane; Crisp, Robert J et al. (2006) Iron-dependent metabolic remodeling in S. cerevisiae. Biochim Biophys Acta 1763:646-51

Philpott, Caroline C (2006) Iron uptake in fungi: a system for every source. Biochim Biophys Acta 1763:636-45

Protchenko, Olga; Rodriguez-Suarez, Roberto; Androphy, Rachel et al. (2006) A screen for genes of heme uptake identifies the FLC family required for import of FAD into the endoplasmic reticulum. J Biol Chem 281:21445-57

Shakoury-Elizeh, Minoo; Tiedeman, John; Rashford, Jared et al. (2004) Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae. Mol Biol Cell 15:1233-43

Protchenko, Olga; Philpott, Caroline C (2003) Regulation of intracellular heme levels by HMX1, a homologue of heme oxygenase, in Saccharomyces cerevisiae. J Biol Chem 278:36582-7

Moore, Robert E; Kim, Youngwoo; Philpott, Caroline C (2003) The mechanism of ferrichrome transport through Arn1p and its metabolism in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 100:5664-9

Pelletier, Benoit; Beaudoin, Jude; Philpott, Caroline C et al. (2003) Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system. Nucleic Acids Res 31:4332-44

Kim, Youngwoo; Yun, Cheol-Won; Philpott, Caroline C (2002) Ferrichrome induces endosome to plasma membrane cycling of the ferrichrome transporter, Arn1p, in Saccharomyces cerevisiae. EMBO J 21:3632-42

Philpott, Caroline C (2002) Molecular aspects of iron absorption: Insights into the role of HFE in hemochromatosis. Hepatology 35:993-1001