ArticleBiochimica et biophysica acta2012
Metabolically induced heteroplasmy shifting and l-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Ebselen restores mitochondrial function through metabolic rewiring in Barth syndrome and related mitochondrial diseases.EMBO molecular medicine · 2026Article
- A review of the link between the lactate-GPR81 axis and mitochondrial angiopathy in MELAS based on imaging characteristics.Journal of neurology · 2025Review
- Article
- Arginine Supplementation in MELAS Syndrome: What Do We Know about the Mechanisms?International journal of molecular sciences · 2024Review
- The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models.International journal of molecular sciences · 2023Review
- Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.Frontiers in neuroscience · 2023Article
- Article
- Review
- Article
- Clinical features, pathogenesis, and management of stroke-like episodes due to MELAS.Metabolic brain disease · 2021Review
- L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency.Nutrients · 2021Article
- Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline.Frontiers in molecular neuroscience · 2021Review
- Ketogenic treatment reduces the percentage of a LHON heteroplasmic mutation and increases mtDNA amount of a LHON homoplasmic mutation.Orphanet journal of rare diseases · 2019Article
- Mutation-specific effects in germline transmission of pathogenic mtDNA variants.Human reproduction (Oxford, England) · 2018Article
- Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems.Annual review of pathology · 2018Review
- Anti-replicative recombinant 5S rRNA molecules can modulate the mtDNA heteroplasmy in a glucose-dependent manner.PloS one · 2018Article
- NO control of mitochondrial function in normal and transformed cells.Biochimica et biophysica acta. Bioenergetics · 2017Review
- Mitochondrial DNA 3243A>G heteroplasmy is associated with changes in cytoskeletal protein expression and cell mechanics.Journal of the Royal Society, Interface · 2017Article
- Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.Molecular genetics and metabolism · 2016Article
- Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The m.3243A>G variant in the mitochondrial tRNA(Leu(UUR)) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of l-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of l-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and l-arginine therapy may constitute promising therapeutic strategies against MELAS.
Indexed as
Identifiers
What OpenQuestion holds
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.