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Mt-Hsp70 Homolog, Ssc2p, Required for Maturation of Yeast Frataxin and Mitochondrial Iron Homeostasis
Open accessAbstract
Here we show that the yeast mitochondrial chaperone Ssc2p, a homolog of mt-Hsp70, plays a critical role in mitochondrial iron homeostasis. Yeast with ssc2-1 mutations were identified by a screen for altered iron-dependent gene regulation and mitochondrial dysfunction. These mutants exhibit increased cellular iron uptake, and the iron accumulates exclusively within mitochondria. Yfh1p is homologous to frataxin, the human protein implicated in the neurodegenerative disease, Friedreich's ataxia. Like mutants of yfh1, ssc2-1 mutants accumulate vast quantities of iron in mitochondria. Furthermore, using import studies with isolated mitochondria, we demonstrate a specific role for Ssc2p in the maturation of Yfh1p within this organelle. This function for a mitochondrial Hsp70 chaperone is likely to be conserved, implying that a human homolog of Ssc2p may be involved in iron homeostasis and in neurodegenerative disease.
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“iron depletion by iron chelators was also shown to enhance lysosome-mediated ferritin degradation (165).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [165]
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Metadata
- Authors
- Knight, S. A. B., Sepuri, N. B. V., Pain, D., & Dancis, A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Dancis, Andrew
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 273
- Issue
- 29
- Pages
- 18389-18393
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1976493565
- Cited by
- 173
- References
- 26
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 2 · 2012: 8
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- W. W. Smith Charitable Trust
- University of Pennsylvania
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- mitochondrial Hsp70, frataxin, mitochondrial iron homeostasis, protein maturation, mitochondrial chaperone, Friedreich's ataxia, iron accumulation, iron absorption, mitochondrial dysfunction, Saccharomyces cerevisiae
- MeSH terms
- Frataxin, Fungal Proteins, Homeostasis, Iron, Mitochondria, Models, Biological, Saccharomyces cerevisiae, Gene Library, Mutagenesis, Site-Directed, Phosphotransferases (Alcohol Group Acceptor), Molecular Chaperones, HSP70 Heat-Shock Proteins, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Iron-Binding Proteins
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