ArticleFree radical biology & medicine2021
Trisomy 21 results in modest impacts on mitochondrial function and central carbon metabolism.
Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- Altered hepatic metabolism in Down syndrome.Cell reports · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Multi-omics insights into immune tolerance at the maternal-fetal interface in recurrent pregnancy loss: mechanisms, integration challenges, and translational perspectives.Frontiers in immunology · 2026Review
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Analysis of genotype effects and inter-individual variability in iPSC-derived trisomy 21 neural progenitor cells.Human molecular genetics · 2025Article
- Metabolomics of mothers of children with autism, idiopathic developmental delay, and Down syndrome.Scientific reports · 2024Article
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- Patterns of Aneuploidy and Signaling Consequences in Cancer.Cancer research · 2024Review
- Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Characterization of mitochondrial and metabolic alterations induced by trisomy 21 during neural differentiation.Free radical biology & medicine · 2023Article
- Dysregulated systemic metabolism in a Down syndrome mouse model.Molecular metabolism · 2023Article
- Evidence of Energy Metabolism Alterations in Cultured Neonatal Astrocytes Derived from the Ts65Dn Mouse Model of Down Syndrome.Brain sciences · 2022Article
- One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage.Frontiers in medicine · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Down syndrome (DS) is the most common genetic cause of intellectual disability. Mechanistically, oxidative stress and mitochondrial dysfunction are reported to be etiological factors for many of the DS-related comorbidities and have previously been reported in a number of in vitro and in vivo models of DS. The purpose of this study was to test for the presence of mitochondrial dysfunction in fibroblast cells obtained via skin biopsy from individuals with DS, and to assess the impact of trisomy 21 on central carbon metabolism. Using extracellular flux assays in matched dermal fibroblasts from euploid and DS individuals, we found that basal mitochondrial dysfunction is quite mild. Stressing the cells with a cocktail of mitochondrial stressors revealed a significant mitochondrial deficit in DS cells compared to euploid controls. Evaluation of extracellular acidification rate did not reveal a baseline abnormality in glycolysis; however, metabolomic assessments utilizing isotopically labeled glucose and glutamine revealed altered central carbon metabolism in DS cells. Specifically, we observed greater glucose dependency, uptake and flux into the oxidative phase of the pentose phosphate pathway in DS fibroblasts. Furthermore, using induced pluripotent stem cells (iPSC) we found that mitochondrial function in DS iPSCs was similar to the previously published studies employing fetal cells. Together, these data indicate that aberrant central carbon metabolism is a candidate mechanism for stress-related mitochondrial dysfunction in DS.
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