Molecular characterization of a copper transport protein in S. cerevisiae: An unexpected role for copper in iron transport
Abstract
We report the identification and characterization of CTR1, a gene in the yeast S. cerevisiae that encodes a multispanning plasma membrane protein specifically required for high affinity copper transport into the cell. The predicted protein contains a methionine- and serine-rich domain that includes 11 examples of the sequence Met-X2-Met, a motif noted in proteins involved in bacterial copper metabolism. CTR1 mutants and deletion strains have profound deficiency in ferrous iron uptake, thus revealing a requirement for copper in mediating ferrous transport into the cell. Genetic evidence suggests that the target for this requirement is the FET3 gene (detailed in a companion study), predicted to encode a copper-containing protein that acts as a cytosolic ferro-oxidase. These findings provide an unexpected mechanistic link between the uptake of copper and iron.
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Overexpression of Fpn enhances ferritin degradation.
“and enhances ferritin degradation (64).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [64]
Only monoubiquitinated ferritin was reported in an Fpn-overexpression experiment.
“Only monoubiquitinated ferritin was reported in an Fpn-overexpression experiment (64).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [64]
Conditions of iron chelation may lead to ferritin degradation through a lysosomal pathway.
“Conditions of iron chelation may lead to ferritin being degraded through a lysosomal pathway (64).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [64]
Depletion of ferritin iron induces monoubiquitination of ferritin subunits.
“Depletion of ferritin iron induces the monoubiquitination of ferritin subunits.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [64]
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“In the yeast Saccharomyces cerevisiae, Fe uptake was found to be dependent on the Cu transport protein CTR1 due to the Cu dependence of the cytosolic ferro-oxidase enzyme FET3 (53).”
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- Authors
- Dancis, A., Yuan, D. S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., & Klausner, R. D.
- Affiliations
- National Institutes of Health (US)
- University of Utah (US)
- University of Minnesota (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1994-01
- Volume
- 76
- Issue
- 2
- Pages
- 393-402
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2007632640
- Cited by
- 659
- References
- 43
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 11 · 2023: 7 · 2022: 15 · 2021: 19 · 2020: 10 · 2019: 10 · 2018: 14 · 2017: 17 · 2016: 11 · 2015: 6 · 2014: 11 · 2013: 19 · 2012: 16
- FWCI
- 43.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- CTR1, copper transport, iron transport, ferrous iron uptake, copper proteins, Saccharomyces cerevisiae
- MeSH terms
- Copper Transporter 1, Amino Acid Sequence, Base Sequence, Biological Transport, Cloning, Molecular, Copper, Ferrous Compounds, Fungal Proteins, Genes, Fungal, Iron, Membrane Proteins, Molecular Sequence Data, Saccharomyces cerevisiae, Sequence Alignment, Sequence Homology, Amino Acid, Cation Transport Proteins, Saccharomyces cerevisiae Proteins
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