Cited by 921Mitochondrial Function and PathologyNeurological diseases and metabolismGenetic Neurodegenerative Diseases

Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin

Babcock, Michael, de Silva, Deepika, Oaks, Robert, Davis-Kaplan, Sandra, Jiralerspong, Sarn, Montermini, Laura, Pandolfo, Massimo, Kaplan, Jerry·1997·Science

Abstract

The gene responsible for Friedreich's ataxia, a disease characterized by neurodegeneration and cardiomyopathy, has recently been cloned and its product designated frataxin. A gene in Saccharomyces cerevisiae was characterized whose predicted protein product has high sequence similarity to the human frataxin protein. The yeast gene (yeast frataxin homolog, YFH1 ) encodes a mitochondrial protein involved in iron homeostasis and respiratory function. Human frataxin also was shown to be a mitochondrial protein. Characterizing the mechanism by which YFH1 regulates iron homeostasis in yeast may help to define the pathologic process leading to cell damage in Friedreich's ataxia.

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Crossref · 10.1126/science.276.5319.1709

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  • Disruption of yeast frataxin homologue YFH1 in yeast strain Δyfh1 induced accumulation of iron in mitochondria and enhanced sensitivity to oxidative stress by H2O2 and iron overload.

    “For instance, the disruption of the yeast frataxin homologue (YFH1) in yeast strain (Δyfh1) induced an accumulation of iron in mitochondria and enhanced their sensitivity to oxidative stress (by H2O2 and iron overload) (13, 93).”
  • Deletion of yeast frataxin homologue YFH1 caused mitochondrial iron accumulation and increased sensitivity to H2O2 toxicity.

    “The first evidence of frataxin's role in mitochondrial iron regulation was obtained by deletion of yeast frataxin homologue, YFH1, and characterization of the yeast phenotype, which revealed that the deletion of YFH1 caused mitochondrial iron accumulation and increased sensitivity to H2O2 toxicity (13).”

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Authors
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J.
Affiliations
  • University of Utah (US)
  • M. Babcock, D. de Silva, R. Oaks, S. Davis-Kaplan, J. Kaplan, Division of Immunology and Cell Biology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Corresponding author
Kaplan, Jerry
Venue
Science
Published
1997-06-13
Volume
276
Issue
5319
Pages
1709-1712
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2069849662
Cited by
921
References
25
Citations by year
2026: 6 · 2025: 12 · 2024: 13 · 2023: 13 · 2022: 25 · 2021: 20 · 2020: 23 · 2019: 16 · 2018: 18 · 2017: 21 · 2016: 22 · 2015: 17 · 2014: 28 · 2013: 38 · 2012: 41
FWCI
18.84
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders
  • National Institutes of Health (5p50dk049219-05, 7r01ns034192-06)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-49219, DK30534)
  • National Institute of Neurological Disorders and Stroke (NS34192)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
frataxin, Friedreich's ataxia, mitochondrial iron accumulation, iron homeostasis, Saccharomyces cerevisiae, mitochondrial proteins, respiratory function, neurodegeneration, cardiomyopathy
MeSH terms
Frataxin, Biological Transport, Carrier Proteins, Cell Membrane, Ceruloplasmin, Cytosol, Friedreich Ataxia, Fungal Proteins, Genes, Fungal, Genetic Complementation Test, Homeostasis, Humans, Iron, Mitochondria, Oxidoreductases, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Transformation, Genetic, Phosphotransferases (Alcohol Group Acceptor), Oxidative Stress, Membrane Transport Proteins, Saccharomyces cerevisiae Proteins, Iron-Binding Proteins

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