ArticleNature communications2021
Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Mitochondrial mutation status, symptom prevalence, and neuroimaging characteristics in MELAS: a systematic review and meta analysis.Orphanet journal of rare diseases · 2026Pooled it
- Inhibition of the mitochondrial pyruvate carrier attenuates the integrated stress response activation in a cellular model of Huntington's disease.Molecular and cellular biochemistry · 2026Article
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Review
- Molecular pathogenesis and gene therapy-based intervention of GTPBP3-related mitochondrial disease.Nature communications · 2026Article
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Targeting mitochondrial deubiquitinase USP30 to induce mitophagy in heteroplasmic mitochondrial diseases.Pharmacological reports : PR · 2026Article
- Relationship between Cellular Oxygen Consumption and Atherosclerosis-associated Mitochondrial Mutations (Variants of the Mitochondrial Genome).Current medicinal chemistry · 2026Article
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Mitochondrial Mutation Leads to Cardiomyocyte Hypertrophy by Disruption of Mitochondria-Associated ER Membrane.Cell proliferation · 2025Article
- Advances in research on mitochondrial dysfunction in neurodegenerative diseases.Journal of neurology · 2025Review
- Metabolic remodeling in hiPSC-derived myofibers carrying the m.3243A>G mutation.Stem cell reports · 2025Article
- Article
- Diabetes Associated With Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype.Diabetes · 2025Review
- Transcriptome sequencing reveals regulatory genes associated with neurogenic hearing loss.BMC medical genomics · 2025Article
- Mitochondrial DNA 3243 mutation may be associated with positivity of zinc transporter 8 autoantibody in cases of slowly progressive type 1 diabetes mellitus.Diabetology international · 2025Article
- Case Report: Abnormal pupils caused by the mitochondrial MT-TL1 gene m.3243A>G mutation.Frontiers in pediatrics · 2025Article
- Ethnicity-related differences in mitochondrial regulation by insulin stimulation in diabetes.Journal of cellular physiology · 2024Review
- Screening for Rare Mitochondrial Genome Variants Reveals a Potentially Novel Association betweenInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy - tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient-derived cells carrying the most prevalent disease related mtDNA mutation, the m.3243 A > G. These studies reveal that the mutation promotes changes in metabolites which are associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 reduced mtDNA mutant load and partially rescued cellular bioenergetic function. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243 A > G mutation.
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Registered trials
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.