ArticleThe Journal of biological chemistry2014
The presence of multiple cellular defects associated with a novel G50E iron-sulfur cluster scaffold protein (ISCU) mutation leads to development of mitochondrial myopathy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 35 citations in OpenAlex.
- Structural heterogeneity of iron-sulfur cluster scaffold protein IscU: Metamorphic or partially folded?Structural dynamics (Melville, N.Y.) · 2026Review
- Nanobodies as tools for studying human frataxin biology.Communications biology · 2026Article
- Stress-induced proteins enhance thermal endurance in soil bacterium Priestia aryabhattai strain PSK.N2.Antonie van Leeuwenhoek · 2025Article
- Admixture and selection offer insights for the conservation and breeding of Guyuan cattle.BMC biology · 2025Article
- Ferrodifferentiation regulates neurodevelopment via ROS generation.Science China. Life sciences · 2023Article
- FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation.Neurology. Genetics · 2022Article
- Mitochondrial iron metabolism and neurodegenerative diseases.Neurotoxicology · 2022Review
- The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases.Genes · 2021Review
- A Highly Conserved Iron-Sulfur Cluster Assembly Machinery between Humans and AmoebaInternational journal of molecular sciences · 2020Article
- Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes.Scientific reports · 2019Article
- Mitochondrial Iron in Human Health and Disease.Annual review of physiology · 2019Review
- Iron-sulfur clusters: from metals through mitochondria biogenesis to disease.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- A novel de novo dominant mutation inJournal of medical genetics · 2017Article
- Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery.The Journal of biological chemistry · 2016Article
- The Eukaryotic-Specific ISD11 Is a Complex-Orphan Protein with Ability to Bind the Prokaryotic IscS.PloS one · 2016Article
- Robust glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI family member protein, is critical for oxidative stress resistance in Saccharomyces cerevisiae.The Journal of biological chemistry · 2015Article
- Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability: IMPLICATIONS IN THE DEVELOPMENT OF MITOCHONDRIAL DISORDER, COXPD19.The Journal of biological chemistry · 2015Article
- Functional implications of the interaction between HscB and IscU in the biosynthesis of FeS clusters.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Iron-sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery.Biochimica et biophysica acta · 2015Review
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Iron-sulfur (Fe-S) clusters are versatile cofactors involved in regulating multiple physiological activities, including energy generation through cellular respiration. Initially, the Fe-S clusters are assembled on a conserved scaffold protein, iron-sulfur cluster scaffold protein (ISCU), in coordination with iron and sulfur donor proteins in human mitochondria. Loss of ISCU function leads to myopathy, characterized by muscle wasting and cardiac hypertrophy. In addition to the homozygous ISCU mutation (g.7044G→C), compound heterozygous patients with severe myopathy have been identified to carry the c.149G→A missense mutation converting the glycine 50 residue to glutamate. However, the physiological defects and molecular mechanism associated with G50E mutation have not been elucidated. In this report, we uncover mechanistic insights concerning how the G50E ISCU mutation in humans leads to the development of severe ISCU myopathy, using a human cell line and yeast as the model systems. The biochemical results highlight that the G50E mutation results in compromised interaction with the sulfur donor NFS1 and the J-protein HSCB, thus impairing the rate of Fe-S cluster synthesis. As a result, electron transport chain complexes show significant reduction in their redox properties, leading to loss of cellular respiration. Furthermore, the G50E mutant mitochondria display enhancement in iron level and reactive oxygen species, thereby causing oxidative stress leading to impairment in the mitochondrial functions. Thus, our findings provide compelling evidence that the respiration defect due to impaired biogenesis of Fe-S clusters in myopathy patients leads to manifestation of complex clinical symptoms.
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