ArticleCommunications biology2025
Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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
8 citing papers in PubMed.
- Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.Neural regeneration research · 2026Article
- Exploration of Metabolic Alterations in Methylmalonic Acidemia across Distinct Genetic Backgrounds.ACS omega · 2026Article
- Disturbances of Mitochondrial Functions and Oxidative Stress Induction in Methylmalonic and Propionic Acidemias: A Critical Role for Metabolite Accumulation.International journal of molecular sciences · 2026Review
- Methylmalonic acid as a ferroptosis-derived danger signal: activation of the PI3K-NF-κB pathway drives M1 macrophage polarization in renal ischemia-reperfusion injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026Review
- Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.Molecular medicine (Cambridge, Mass.) · 2025Review
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- iPSC-derived cerebral organoids reveal mitochondrial, inflammatory and neuronal vulnerabilities in bipolar disorder.Translational psychiatry · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Methylmalonic aciduria (MMA) is an inborn error of metabolism resulting in loss of function of the enzyme methylmalonyl-CoA mutase (MMUT). Despite acute and persistent neurological symptoms, the pathogenesis of MMA in the central nervous system is poorly understood, which has contributed to a dearth of effective brain specific treatments. Here we utilised patient-derived induced pluripotent stem cells and in vitro differentiation to generate a human neuronal model of MMA. We reveal strong evidence of mitochondrial dysfunction caused by deficiency of MMUT in patient neurons. By employing patch-clamp electrophysiology, targeted metabolomics, and bulk transcriptomics, we expose an altered state of excitability, which is exacerbated by application of dimethyl-2-oxoglutarate, and we suggest may be connected to metabolic rewiring. Our work provides first evidence of mitochondrial driven neuronal dysfunction in MMA, which through our comprehensive characterisation of this paradigmatic model, enables first steps to identifying effective therapies.
Indexed as
Identifiers
What Socratic 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 Socratic graph.