Frataxin interacts functionally with mitochondrial electron transport chain proteins
Abstract
Frataxin deficiency is the main cause of Friedreich ataxia, an autosomal recessive neurodegenerative disorder. Frataxin function in mitochondria has not been fully explained yet. In this work, we show that Saccharomyces cerevisiae frataxin orthologue Yfh1p interacts physically with succinate dehydrogenase complex subunits Sdh1p and Sdh2p of the yeast mitochondrial electron transport chain and also with electron transfer flavoprotein complex ETFalpha and ETFbeta subunits from the electron transfer flavoprotein complex. Genetic synthetic interaction experiments confirmed a functional relationship between YFH1 and succinate dehydrogenase genes SDH1 and SDH2. We also demonstrate a physical interaction between human frataxin and human succinate dehydrogenase complex subunits, suggesting also a key role of frataxin in the mitochondrial electron transport chain in humans. Consequently, we suggest a direct participation of the respiratory chain in the pathogenesis of the Friedreich ataxia, which we propose to be considered as an OXPHOS disease.
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In stable HeLa cell lines transfected with a GFP reporter containing a GAA:TTC repeat expansion (GAA-148 repeats), 5 to 50 μM of small molecules such as diminazene, distamycin, pentamidine, DAPI, and Hoescht 33258 increase GFP expression by >20-fold.
“Similarly, by using stable HeLa cell lines transfected with a GFP reporter containing a GAA:TTC repeat expansion (GAA-148 repeats), 5 to 50 μM of small molecules such as diminazene, distamycin, pentamidine, DAPI, and Hoescht 33258 have been shown to increase GFP expression by >20-fold (109).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [109]
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- Authors
- González-Cabo, P., Vázquez-Manrique, R. P., García-Gimeno, M. A., Sanz, P., & Palau, F.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-16
- Volume
- 14
- Issue
- 15
- Pages
- 2091-2098
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2122729932
- Cited by
- 140
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 2 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 5 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- frataxin, Friedreich's ataxia, mitochondrial electron transport chain, succinate dehydrogenase complex, electron transfer flavoprotein, protein-protein interaction, synthetic genetic interactions, Saccharomyces cerevisiae, mitochondrial respiratory chain
- MeSH terms
- Frataxin, Humans, Mitochondria, Protein Binding, Saccharomyces cerevisiae, Succinate Dehydrogenase, Gene Expression Regulation, Fungal, Iron-Binding Proteins, Electron Transport Chain Complex Proteins
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