ArticleAmerican journal of human genetics2011
A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins.
Article in American journal of human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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143 citing papers in PubMed, 279 citations in OpenAlex.
- Expanding the phenotype of IBA57 mutations: related leukodystrophy can remain asymptomatic.Journal of human genetics · 2018Trial
- Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy.European journal of human genetics : EJHG · 2014Trial
- Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes.Cell death discovery · 2026Article
- Mitochondrial dysfunction-induced hemolysis: a precursor to vascular leakage and pulmonary hypertension.Blood vessels, thrombosis & hemostasis · 2025Article
- Structural basis for catalysis by human lipoyl synthase.Nature communications · 2025Article
- Functional Relationships of Two NFU Proteins in Maintaining the Abundances of Mitochondrial Iron-Sulfur Proteins.Plant direct · 2025Article
- Mitochondria as a primary determinant of angiogenic modality in pulmonary arterial hypertension.The Journal of experimental medicine · 2024Article
- Clinical, biochemical and molecular characterization of a new case withJIMD reports · 2024Article
- Recent progress of methods for cuproptosis detection.Frontiers in molecular biosciences · 2024Review
- BOLA3 and NFU1 link mitoribosome iron-sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome.Nucleic acids research · 2023Article
- Biochemical characterization of patients with dihydrolipoamide dehydrogenase deficiency.JIMD reports · 2023Article
- Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway.Journal of molecular biology · 2023Article
- Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?International journal of molecular sciences · 2023Review
- Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1.Disease models & mechanisms · 2023Article
- A novel IBA57 variant is associated with mitochondrial iron-sulfur protein deficiency and necrotizing myelopathy in dogs.Frontiers in genetics · 2023Article
- Mitochondrial Dysfunction: Pathophysiology and Mitochondria-Targeted Drug Delivery Approaches.Pharmaceutics · 2022Review
- In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1.ACS bio & med chem Au · 2022Article
- Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry.International journal of molecular sciences · 2022Article
- The ataxia-telangiectasia mutated gene product regulates the cellular acid-labile sulfide fraction.DNA repair · 2022Article
- Molecular Basis of Rare Diseases Associated to the Maturation of Mitochondrial [4Fe-4S]-Containing Proteins.Biomolecules · 2022Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report on ten individuals with a fatal infantile encephalopathy and/or pulmonary hypertension, leading to death before the age of 15 months. Hyperglycinemia and lactic acidosis were common findings. Glycine cleavage system and pyruvate dehydrogenase complex (PDHC) activities were low. Homozygosity mapping revealed a perfectly overlapping homozygous region of 1.24 Mb corresponding to chromosome 2 and led to the identification of a homozygous missense mutation (c.622G > T) in NFU1, which encodes a conserved protein suggested to participate in Fe-S cluster biogenesis. Nine individuals were homozygous for this mutation, whereas one was compound heterozygous for this and a splice-site (c.545 + 5G > A) mutation. The biochemical phenotype suggested an impaired activity of the Fe-S enzyme lipoic acid synthase (LAS). Direct measurement of protein-bound lipoic acid in individual tissues indeed showed marked decreases. Upon depletion of NFU1 by RNA interference in human cell culture, LAS and, in turn, PDHC activities were largely diminished. In addition, the amount of succinate dehydrogenase, but no other Fe-S proteins, was decreased. In contrast, depletion of the general Fe-S scaffold protein ISCU severely affected assembly of all tested Fe-S proteins, suggesting that NFU1 performs a specific function in mitochondrial Fe-S cluster maturation. Similar biochemical effects were observed in Saccharomyces cerevisiae upon deletion of NFU1, resulting in lower lipoylation and SDH activity. Importantly, yeast Nfu1 protein carrying the individuals' missense mutation was functionally impaired. We conclude that NFU1 functions as a late-acting maturation factor for a subset of mitochondrial Fe-S proteins.
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