ArticleProceedings of the National Academy of Sciences of the United States of America2013
Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.
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Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Efficacy of neurofeedback in the treatment of Dyslexia: a systematic review.Annals of dyslexia · 2026Pooled it
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.Nature communications · 2026Article
- Patient specific regulation of metabolism and cell death pathways in m.3243A>G mutated iPS-cells.Scientific reports · 2026Article
- Impaired mitochondrial morphology and respiratory dysfunction in human induced pluripotent stem cells with mitochondrial tRNA mutations (m.3243A>G and m.14739G>A).Orphanet journal of rare diseases · 2026Article
- Towards CRISPR-based editing of the mitochondrial genome in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Insights into PINK1/Parkin function and dysfunction from Drosophila models.The Biochemical journal · 2025Review
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- Article
- Metabolic remodeling in hiPSC-derived myofibers carrying the m.3243A>G mutation.Stem cell reports · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Preclinical models of mitochondrial dysfunction: mtDNA and nuclear-encoded regulators in diverse pathologies.Frontiers in aging · 2025Review
- Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: achievements and weaknesses.Frontiers in cellular neuroscience · 2024Review
- The NADInternational journal of biological sciences · 2024Article
- T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants.Life science alliance · 2023Article
- Mitophagy in yeast: known unknowns and unknown unknowns.The Biochemical journal · 2023Review
- Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations.Journal of biomedical science · 2023Review
- The pyruvate dehydrogenase complex regulates mitophagic trafficking and protein phosphorylation.Life science alliance · 2023Article
- The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models.International journal of molecular sciences · 2023Review
- Mitochondrial heterogeneity in diseases.Signal transduction and targeted therapy · 2023Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA (mtDNA) mutations manifest with vast clinical heterogeneity. The molecular basis of this variability is mostly unknown because the lack of model systems has hampered mechanistic studies. We generated induced pluripotent stem cells from patients carrying the most common human disease mutation in mtDNA, m.3243A>G, underlying mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. During reprogramming, heteroplasmic mtDNA showed bimodal segregation toward homoplasmy, with concomitant changes in mtDNA organization, mimicking mtDNA bottleneck during epiblast specification. Induced pluripotent stem cell-derived neurons and various tissues derived from teratomas manifested cell-type specific respiratory chain (RC) deficiency patterns. Similar to MELAS patient tissues, complex I defect predominated. Upon neuronal differentiation, complex I specifically was sequestered in perinuclear PTEN-induced putative kinase 1 (PINK1) and Parkin-positive autophagosomes, suggesting active degradation through mitophagy. Other RC enzymes showed normal mitochondrial network distribution. Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis.
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