ArticleBiomedicines2022
Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure.
Article in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 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
- Clinical Efficacy and Safety of the Ketogenic Diet in Patients with Genetic Confirmation of Drug-Resistant Epilepsy.Nutrients · 2025Review
- The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization.International journal of molecular sciences · 2025Review
- Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.EMBO reports · 2024Article
- Diagnosis and Management of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes Syndrome.Biomolecules · 2024Review
- Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems.CNS neuroscience & therapeutics · 2024Review
- Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.European journal of case reports in internal medicine · 2024Article
- Nutritional Approach in Selected Inherited Metabolic Cardiac Disorders-A Concise Summary of Available Scientific Evidence.Nutrients · 2023Review
- The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models.International journal of molecular sciences · 2023Review
- Pathophysiology of Cerebellar Degeneration in Mitochondrial Disorders: Insights from theInternational journal of molecular sciences · 2023Article
- Creation of Mitochondrial Disease Models Using Mitochondrial DNA Editing.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
(1) Background: The development of mitochondrial medicine has been severely impeded by a lack of effective therapies. (2) Methods: To better understand Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-like episodes (MELAS) syndrome, neuronal cybrid cells carrying different mutation loads of the m.3243A > G mitochondrial DNA variant were analysed using a multi-omic approach. (3) Results: Specific metabolomic signatures revealed that the glutamate pathway was significantly increased in MELAS cells with a direct correlation between glutamate concentration and the m.3243A > G heteroplasmy level. Transcriptomic analysis in mutant cells further revealed alterations in specific gene clusters, including those of the glutamate, gamma-aminobutyric acid pathways, and tricarboxylic acid (TCA) cycle. These results were supported by post-mortem brain tissue analysis from a MELAS patient, confirming the glutamate dysregulation. Exposure of MELAS cells to ketone bodies significantly reduced the glutamate level and improved mitochondrial functions, reducing the accumulation of several intermediate metabolites of the TCA cycle and alleviating the NADH-redox imbalance. (4) Conclusions: Thus, a multi-omic integrated approach to MELAS cells revealed glutamate as a promising disease biomarker, while also indicating that a ketogenic diet should be tested in MELAS patients.
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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.