ArticleAmerican journal of human genetics2016
Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers.
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74 citing papers in PubMed, 125 citations in OpenAlex.
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- Mitochondrial succinate transport is required for cardiac ischaemia/reperfusion injury.Cardiovascular research · 2026Article
- From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026Review
- Establishment and validation of a prognostic model for oral squamous cell carcinoma based on ribosomal and apoptosis-related gene expression.Discover oncology · 2026Article
- Mitochondrial proteostasis regulated by CRL5Communications biology · 2025Article
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Expanding the Allelic and Clinical Heterogeneity of Movement Disorders Linked to Defects of Mitochondrial Adenosine Triphosphate Synthase.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Mitochondrial medicine: "from bench to bedside" 3PM-guided concept.The EPMA journal · 2025Article
- Network architecture of transcriptomic stress responses in zebrafish embryos.PLoS computational biology · 2025Article
- Genome-Related Mechanisms Contributing to Differences in Alzheimer's Disease Incidence Between White and Black Older US Adults.Journal of racial and ethnic health disparities · 2025Article
- Dietary effects on the retina of hamsters.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Modeling the different conformations of the human mitochondrial ADP/ATP carrier using AlphaFold and molecular dynamics simulations of the protein-ligand complexes.Computational and structural biotechnology journal · 2025Article
- BiallelicBrain communications · 2025Article
- Mitochondrial DNA depletion syndrome and its cardiac complication.Frontiers in cardiovascular medicine · 2025Review
- Transcriptomic Profiling Reveals Altered Expression of Genes Involved in Metabolic and Immune Processes in NDV-Infected Chicken Embryos.Metabolites · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 18 institutions in 7 countries.
Funding
Abstract
Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations. All affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle. Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of the seven subjects, and the other three case subjects harbored the same c.703C>G (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of AAC1 protein levels and loss of respiratory chain complexes containing mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant proteins are severely impaired in ADP/ATP transport, affecting most likely the substrate binding and mechanics of the carrier, respectively. This highly reduced capacity for transport probably affects mitochondrial DNA maintenance and in turn respiration, causing a severe energy crisis. The confirmation of the pathogenicity of these de novo SLC25A4 mutations highlights a third distinct clinical phenotype associated with mutation of this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo mutations, which has significant implications for the application and analysis of whole-exome sequencing data in mitochondrial disease.
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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.