ArticleHuman molecular genetics2015
Characterization of clinically identified mutations in NDUFV1, the flavin-binding subunit of respiratory complex I, using a yeast model system.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Molecular Alterations in Core Subunits of Mitochondrial Complex I and Their Relation to Parkinson's Disease.Molecular neurobiology · 2025Review
- Fluorescence lifetime imaging microscopy of endogenous fluorophores in health and disease.Journal of muscle research and cell motility · 2025Review
- Proton-Translocating NADH-Ubiquinone Oxidoreductase: Interaction with Artificial Electron Acceptors, Inhibitors, and Potential Medicines.International journal of molecular sciences · 2024Review
- Integrative bioinformatics approach yields a novel gene expression risk model for prognosis and progression prediction in prostate cancer.Journal of cellular and molecular medicine · 2024Article
- Regulation of respiratory complex I assembly by FMN cofactor targeting.Redox biology · 2024Article
- Article
- Isoforms of the transcriptional cofactor SIN3 differentially regulate genes necessary for energy metabolism and cell survival.Biochimica et biophysica acta. Molecular cell research · 2022Article
- Reverse Electron Transfer by Respiratory Complex I Catalyzed in a Modular Proteoliposome System.Journal of the American Chemical Society · 2022Article
- Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer.Signal transduction and targeted therapy · 2022Article
- Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I.Scientific reports · 2021Article
- [A novel frameshift NDUFV1 mutation in a child with the phenotype of optic nerve atrophy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Cork-in-bottle mechanism of inhibitor binding to mammalian complex I.Science advances · 2021Article
- The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases.Genes · 2021Review
- NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms.Genetics and molecular biology · 2021Article
- Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies ofLife (Basel, Switzerland) · 2020Review
- Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation.Nature structural & molecular biology · 2020Article
- Mutations inCells · 2019Article
- Redox-Dependent Loss of Flavin by Mitochondrial Complex I in Brain Ischemia/Reperfusion Injury.Antioxidants & redox signaling · 2019Article
- Energetics and Dynamics of Proton-Coupled Electron Transfer in the NADH/FMN Site of Respiratory Complex I.Journal of the American Chemical Society · 2019Article
- AFrontiers in genetics · 2019Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Dysfunctions in mitochondrial complex I (NADH:ubiquinone oxidoreductase) are both genetically and clinically highly diverse and a major cause of human mitochondrial diseases. The genetic determinants of individual clinical cases are increasingly being described, but how these genetic defects affect complex I on the molecular and cellular level, and have different clinical consequences in different individuals, is little understood. Furthermore, without molecular-level information innocent genetic variants may be misassigned as pathogenic. Here, we have used a yeast model system (Yarrowia lipolytica) to study the molecular consequences of 16 single amino acid substitutions, classified as pathogenic, in the NDUFV1 subunit of complex I. NDUFV1 binds the flavin cofactor that oxidizes NADH and is the site of complex I-mediated reactive oxygen species production. Seven mutations caused loss of complex I expression, suggesting they are detrimental but precluding further study. In two variants complex I was fully assembled but did not contain any flavin, and four mutations led to functionally compromised enzymes. Our study provides a molecular rationale for assignment of all these variants as pathogenic. However, three variants provided complex I that was functionally equivalent to the wild-type enzyme, challenging their assignment as pathogenic. By combining structural, bioinformatic and functional data, a simple scoring system for the initial evaluation of future NDUFV1 variants is proposed. Overall, our results broaden understanding of how mutations in this centrally important core subunit of complex I affect its function and provide a basis for understanding the role of NDUFV1 mutations in mitochondrial dysfunction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.