ArticleThe Journal of biological chemistry2013
Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 95 citations in OpenAlex.
- Anti-gene oligonucleotides targeting Friedreich's ataxia expanded GAA⋅TTC repeats increase Frataxin expression.Molecular therapy. Nucleic acids · 2025Article
- Frataxin: from the sequence to the biological role.Biophysical reviews · 2025Review
- Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis.Biochemistry · 2025Article
- Functional characterization of FvCAMTA1in salt stress response ofFrontiers in plant science · 2025Article
- Quantification of human mature frataxin protein expression in nonhuman primate hearts after gene therapy.Communications biology · 2023Article
- Large-scale expansions of Friedreich's ataxia GAA•TTC repeats in an experimental human system: role of DNA replication and prevention by LNA-DNA oligonucleotides and PNA oligomers.Nucleic acids research · 2023Article
- Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.Epigenomes · 2023Article
- Cardiac Involvement in Mitochondrial Disorders.Current heart failure reports · 2023Review
- Article
- Yeast cells depleted of the frataxin homolog Yfh1 redistribute cellular iron: Studies using Mössbauer spectroscopy and mathematical modeling.The Journal of biological chemistry · 2022Article
- Posttranslational regulation of mitochondrial frataxin and identification of compounds that increase frataxin levels in Friedreich's ataxia.The Journal of biological chemistry · 2022Article
- Predicting Mitochondrial Dynamic Behavior in Genetically Defined Neurodegenerative Diseases.Cells · 2022Review
- During FeS cluster biogenesis, ferredoxin and frataxin use overlapping binding sites on yeast cysteine desulfurase Nfs1.The Journal of biological chemistry · 2022Article
- Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich's Ataxia.Frontiers in neuroscience · 2022Review
- Iron-Sulfur Cluster Biogenesis as a Critical Target in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Molecular Details of the Frataxin-Scaffold Interaction during Mitochondrial Fe-S Cluster Assembly.International journal of molecular sciences · 2021Review
- Future Prospects of Gene Therapy for Friedreich's Ataxia.International journal of molecular sciences · 2021Review
- Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Metabolism.Frontiers in cell and developmental biology · 2021Review
- Iron-Sulfur Cluster Complex Assembly in the Mitochondria ofPlants (Basel, Switzerland) · 2020Article
- Unique roles of iron and zinc binding to the yeast Fe-S cluster scaffold assembly protein "Isu1".Metallomics : integrated biometal science · 2019Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
For iron-sulfur (Fe-S) cluster synthesis in mitochondria, the sulfur is derived from the amino acid cysteine by the cysteine desulfurase activity of Nfs1. The enzyme binds the substrate cysteine in the pyridoxal phosphate-containing site, and a persulfide is formed on the active site cysteine in a manner depending on the accessory protein Isd11. The persulfide is then transferred to the scaffold Isu, where it combines with iron to form the Fe-S cluster intermediate. Frataxin is implicated in the process, although it is unclear where and how, and deficiency causes Friedreich ataxia. Using purified proteins and isolated mitochondria, we show here that the yeast frataxin homolog (Yfh1) directly and specifically stimulates cysteine binding to Nfs1 by exposing substrate-binding sites. This novel function of frataxin does not require iron, Isu1, or Isd11. Once bound to Nfs1, the substrate cysteine is the source of the Nfs1 persulfide, but this step is independent of frataxin and strictly dependent on Isd11. Recently, a point mutation in Isu1 was found to bypass many frataxin functions. The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity. We propose a regulatory mechanism for the Nfs1 persulfide-forming activity. Specifically, at least two separate conformational changes must occur in the enzyme for optimum activity as follows: one is mediated by frataxin interaction that exposes the "buried" substrate-binding sites, and the other is mediated by Isd11 interaction that brings the bound substrate cysteine and the active site cysteine in proximity for persulfide formation.
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