ArticleJournal of molecular biology2017
Understanding the Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 1 (MMDS1)-Impact of a Disease-Causing Gly208Cys Substitution on Structure and Activity of NFU1 in the Fe/S Cluster Biosynthetic Pathway.
Article in Journal of molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- BOLA3 and NFU1 link mitoribosome iron-sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome.Nucleic acids research · 2023Article
- Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1.Disease models & mechanisms · 2023Article
- In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1.ACS bio & med chem Au · 2022Article
- Molecular Basis of Rare Diseases Associated to the Maturation of Mitochondrial [4Fe-4S]-Containing Proteins.Biomolecules · 2022Review
- A Review of Multiple Mitochondrial Dysfunction Syndromes, Syndromes Associated with Defective Fe-S Protein Maturation.Biomedicines · 2021Review
- Allele-specific mitochondrial stress induced by Multiple Mitochondrial Dysfunctions Syndrome 1 pathogenic mutations modeled in Caenorhabditis elegans.PLoS genetics · 2021Article
- Biochemical impact of a disease-causing Ile67Asn substitution on BOLA3 protein.Metallomics : integrated biometal science · 2021Article
- Assembly of the [4Fe-4S] cluster of NFU1 requires the coordinated donation of two [2Fe-2S] clusters from the scaffold proteins, ISCU2 and ISCA1.Human molecular genetics · 2020Article
- Rats with a Human Mutation of NFU1 Develop Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Reconstitution, characterization, and [2Fe-2S] cluster exchange reactivity of a holo human BOLA3 homodimer.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- The Role of Iron Regulation in Immunometabolism and Immune-Related Disease.Frontiers in molecular biosciences · 2019Review
- Role of the HSPA9/HSC20 chaperone pair in promoting directional human iron-sulfur cluster exchange involving monothiol glutaredoxin 5.Journal of inorganic biochemistry · 2018Article
- Iron-sulfur cluster biosynthesis and trafficking - impact on human disease conditions.Metallomics : integrated biometal science · 2018Review
- Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex.The FEBS journal · 2018Article
- Understanding the molecular basis for multiple mitochondrial dysfunctions syndrome 1 (MMDS1): impact of a disease-causing Gly189Arg substitution on NFU1.The FEBS journal · 2017Article
- Privileged Electrophile Sensors: A Resource for Covalent Drug Development.Cell chemical biology · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Iron-sulfur (Fe/S)-cluster-containing proteins constitute one of the largest protein classes, with varied functions that include electron transport, regulation of gene expression, substrate binding and activation, and radical generation. Consequently, the biosynthetic machinery for Fe/S clusters is evolutionarily conserved, and mutations in a variety of putative intermediate Fe/S cluster scaffold proteins can cause disease states, including multiple mitochondrial dysfunctions syndrome (MMDS), sideroblastic anemia, and mitochondrial encephalomyopathy. Herein, we have characterized the impact of defects occurring in the MMDS1 disease state that result from a point mutation (Gly208Cys) near the active site of NFU1, an Fe/S scaffold protein, via an in vitro investigation into the structural and functional consequences. Analysis of protein stability and oligomeric state demonstrates that the mutant increases the propensity to dimerize and perturbs the secondary structure composition. These changes appear to underlie the severely decreased ability of mutant NFU1 to accept an Fe/S cluster from physiologically relevant sources. Therefore, the point mutation on NFU1 impairs downstream cluster trafficking and results in the disease phenotype, because there does not appear to be an alternative in vivo reconstitution path, most likely due to greater protein oligomerization from a minor structural change.
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Registered trials
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