ArticleDiabetologia2006
Diabetes-associated mitochondrial DNA mutation A3243G impairs cellular metabolic pathways necessary for beta cell function.
Article in Diabetologia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 98 citations in OpenAlex.
- Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm.Diabetes, obesity & metabolism · 2026Review
- Melatonin alleviates oxidative stress induced damage in human iPSCs harboring mtDNA 3243A>G mutation via MAPK pathway.Stem cell research & therapy · 2025Article
- Diabetes Associated With Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype.Diabetes · 2025Review
- Serum metabolomics signature of maternally inherited diabetes and deafness by gas chromatography-time of flight mass spectrometry.Journal of diabetes investigation · 2025Article
- The mitochondrial tRNA-derived fragment, mt-tRF-LeuMolecular metabolism · 2024Article
- Mitochondrial Dynamics and Insulin Secretion.International journal of molecular sciences · 2023Review
- The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models.International journal of molecular sciences · 2023Review
- Review
- Review
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- Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation.Nature communications · 2021Article
- African and Asian Mitochondrial DNA Haplogroups Confer Resistance Against Diabetic Stresses on Retinal Pigment Epithelial Cybrid Cells In Vitro.Molecular neurobiology · 2020Article
- Polycystic ovary syndrome dependency on mtDNA mutation; copy Number and its association with insulin resistance.BMC research notes · 2019Article
- mTORC1 is required for expression of LRPPRC and cytochrome-American journal of physiology. Cell physiology · 2019Article
- Quantitative Variation in m.3243A > G Mutation Produce Discrete Changes in Energy Metabolism.Scientific reports · 2019Article
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- Mitochondrial Transfer of Wharton's Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts.Oxidative medicine and cellular longevity · 2019Article
- Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes.Lipids in health and disease · 2018Article
- The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane.Cell death & disease · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisMitochondrial DNA (mtDNA) mutations cause several diseases, including mitochondrial inherited diabetes and deafness (MIDD), typically associated with the mtDNA A3243G point mutation on tRNALeu gene. The common hypothesis to explain the link between the genotype and the phenotype is that the mutation might impair mitochondrial metabolism expressly required for beta cell functions. However, this assumption has not yet been tested.
methodsWe used clonal osteosarcoma cytosolic hybrid cells (namely cybrids) harbouring mitochondria derived from MIDD patients and containing either exclusively wild-type or mutated (A3243G) mtDNA. According to the importance of mitochondrial metabolism in beta cells, we studied the impact of the mutation on key parameters by comparing stimulation of these cybrids by the main insulin secretagogue glucose and the mitochondrial substrate pyruvate.
resultsCompared with control mtDNA from the same patient, the A3243G mutation markedly modified metabolic pathways leading to a high glycolytic rate (2.8-fold increase), increased lactate production (2.5-fold), and reduced glucose oxidation (-83%). We also observed impaired NADH responses (-56%), negligible mitochondrial membrane potential, and reduced, only transient ATP generation. Moreover, cybrid cells carrying patient-derived mutant mtDNA exhibited deranged cell calcium handling with increased cytosolic loads (1.4-fold higher), and elevated reactive oxygen species (2.6-fold increase) under glucose deprivation. CONCLUSIONS/
interpretationThe present study demonstrates that the mtDNA A3243G mutation impairs crucial metabolic events required for proper cell functions, such as coupling of glucose recognition to insulin secretion.
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