ArticleHuman molecular genetics2013
Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Mapping the Diverse Genetic Disorders and Rare Diseases Among the Syrian Population: Implications on Refugee Health and Health Services in Host Countries.Journal of immigrant and minority health · 2020Pooled it
- Clinical presentation and genotype-phenotype correlation of a novel pure duplication of 6p25.2-p22.3: a case report and literature review.Molecular cytogenetics · 2026Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Integrated cross-species translation and biophysical multi-scale modeling links molecular signatures and locomotory phenotypes in spaceflight-induced sarcopenia.NPJ microgravity · 2026Article
- NFS1 Plays a Critical Role in Regulating Ferroptosis Homeostasis.Biomolecules · 2025Review
- Integrated Cross-Species Translation and Biophysical Multi-Scale Modeling Links Molecular Signatures and Locomotory Phenotypes in Spaceflight-Induced Sarcopenia.bioRxiv : the preprint server for biology · 2025Article
- Review
- Iron-Sulfur Clusters and Iron Responsive Element Binding Proteins Mediate Iron Accumulation in Corneal Endothelial Cells in Fuchs Dystrophy.Investigative ophthalmology & visual science · 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
- Evolution is in the details: Regulatory differences in modern human and Neanderthal.Computational and structural biotechnology journal · 2025Article
- High LYRM4-AS1 predicts poor prognosis in patients with glioma and correlates with immune infiltration.PeerJ · 2023Article
- Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease.Human molecular genetics · 2022Article
- Mammalian iron sulfur cluster biogenesis and human diseases.IUBMB life · 2022Article
- Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes.Human mutation · 2022Article
- Double-edge sword roles of iron in driving energy production versus instigating ferroptosis.Cell death & disease · 2022Review
- Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer.Oxidative medicine and cellular longevity · 2022Review
- Inborn errors of metabolism associated with 3-methylglutaconic aciduria.Clinica chimica acta; international journal of clinical chemistry · 2021Review
- Adaptation of the heart to Frataxin depletion: Evidence that integrated stress response can predominate over mTORC1 activation.Human molecular genetics · 2021Article
- Iron-Sulfur Cluster Biogenesis as a Critical Target in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
Iron-sulfur clusters (ISCs) are important prosthetic groups that define the functions of many proteins. Proteins with ISCs (called iron-sulfur or Fe-S proteins) are present in mitochondria, the cytosol, the endoplasmic reticulum and the nucleus. They participate in various biological pathways including oxidative phosphorylation (OXPHOS), the citric acid cycle, iron homeostasis, heme biosynthesis and DNA repair. Here, we report a homozygous mutation in LYRM4 in two patients with combined OXPHOS deficiency. LYRM4 encodes the ISD11 protein, which forms a complex with, and stabilizes, the sulfur donor NFS1. The homozygous mutation (c.203G>T, p.R68L) was identified via massively parallel sequencing of >1000 mitochondrial genes (MitoExome sequencing) in a patient with deficiency of complexes I, II and III in muscle and liver. These three complexes contain ISCs. Sanger sequencing identified the same mutation in his similarly affected cousin, who had a more severe phenotype and died while a neonate. Complex IV was also deficient in her skeletal muscle. Several other Fe-S proteins were also affected in both patients, including the aconitases and ferrochelatase. Mutant ISD11 only partially complemented for an ISD11 deletion in yeast. Our in vitro studies showed that the l-cysteine desulfurase activity of NFS1 was barely present when co-expressed with mutant ISD11. Our findings are consistent with a defect in the early step of ISC assembly affecting a broad variety of Fe-S proteins. The differences in biochemical and clinical features between the two patients may relate to limited availability of cysteine in the newborn period and suggest a potential approach to therapy.
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