ArticleMolecular genetics and metabolism2018
Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome.
Article in Molecular genetics and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Global mitochondrial connectivity map reveals the landscape of yeast functional assemblies and conserved protein communities.Nature communications · 2026Article
- Review
- Variants in Human ATP Synthase Mitochondrial Genes: Biochemical Dysfunctions, Associated Diseases, and Therapies.International journal of molecular sciences · 2024Review
- Dysfunctional Postnatal Mitochondrial Energy Metabolism in a Patient with Neurodevelopmental Defects Caused by Intrauterine Growth Restriction Due to Idiopathic Placental Insufficiency.International journal of molecular sciences · 2024Article
- Letter to the Editor: Depending on the Disease Stage and Modifying Factors, mtDNA-Associated Hearing Loss Can Occur With Many mtDNA Mutations.Journal of Korean medical science · 2024Article
- Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease.Pharmaceutics · 2022Review
- Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.Development (Cambridge, England) · 2022Article
- Metabolic reprogramming: a bridge between aging and tumorigenesis.Molecular oncology · 2022Review
- Article
- Clinical Insights into Mitochondrial Neurodevelopmental and Neurodegenerative Disorders: Their Biosignatures from Mass Spectrometry-Based Metabolomics.Metabolites · 2021Review
- Leigh Syndrome: A Tale of Two Genomes.Frontiers in physiology · 2021Review
- Genetic and Mitochondrial Metabolic Analyses of an Atypical Form of Leigh Syndrome.Frontiers in cell and developmental biology · 2021Article
- Molecular genetic and mitochondrial metabolic analyses confirm the suspected mitochondrial etiology in a pediatric patient with an atypical form of alternating hemiplegia of childhood.Molecular genetics and metabolism reports · 2020Article
- The nuclear background influences the penetrance of the near-homoplasmic m.1630 A > G MELAS variant in a symptomatic proband and asymptomatic mother.Molecular genetics and metabolism · 2019Article
- Novel metabolic signatures of compound heterozygousClinical case reports · 2018Article
- Vaccination triggering onset of m.8993T > G associated Leigh syndrome.Molecular genetics and metabolism reports · 2018Article
- Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993T>G variant.Molecular genetics and metabolism reports · 2018Article
- Maternally inherited mitochondrial respiratory disorders: from pathogenetic principles to therapeutic implications.Molecular genetics and metabolismReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
In this study, we report a novel perpective of metabolic consequences for the m.8993T>G variant using fibroblasts from a proband with clinical symptoms compatible with Maternally Inherited Leigh Syndrome (MILS). Definitive diagnosis was corroborated by mitochondrial DNA testing for the pathogenic variant m.8993T>G in MT-ATP6 subunit by Sanger sequencing. The long-range PCR followed by massively parallel sequencing method detected the near homoplasmic m.8993T>G variant at 83% in the proband's fibroblasts and at 0.4% in the mother's fibroblasts. Our results are compatible with very low levels of germline heteroplasmy or an apparent de novo mutation. Our mitochondrial morphometric analysis reveals severe defects in mitochondrial cristae structure in the proband's fibroblasts. Our live-cell mitochondrial respiratory analyses show impaired oxidative phosphorylation with decreased spare respiratory capacity in response to energy stress in the proband's fibroblasts. We detected a diminished glycolysis with a lessened glycolytic capacity and reserve, revealing a stunted ability to switch to glycolysis upon full inhibition of OXPHOS activities. This dysregulated energy reprogramming results in a defective interplay between OXPHOS and glycolysis during an energy crisis. Our study sheds light on the potential pathophysiologic mechanism leading to chronic energy crisis in this MILS patient harboring the m.8993T>G variant.
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