ArticleNature metabolism2023
Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- 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
- Revolutionizing neonatal health: India's journey from assays to advanced genetics.Journal of applied genetics · 2026Review
- Amino Acid Deficiency Secondary to Continuous Venovenous Hemofiltration in Acute Decompensation of Organic Acidemias: An Anabolic Dead End?Critical care explorations · 2026Observational
- Untargeted metabolomics reveals distinct metabolic profiles in MUT-type methylmalonic acidemia.Molecular and cellular pediatrics · 2026Article
- A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy.Nature communications · 2026Article
- Immune Dysregulation in Branched Chain Organic Acidemias.Journal of inherited metabolic disease · 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
- [N-carbamylglutamate in the treatment of neonatal organic acidemia crisis: a report of five cases].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C Disease.JIMD reports · 2026Article
- Expanding the genetic landscape of inherited metabolic diseases using long-read sequencing and transcriptomic profiling.European journal of human genetics : EJHG · 2026Article
- SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism.Cell reports. Medicine · 2026Article
- Cooperative Architecture of Mitochondrial Proteome Homeostasis.medRxiv : the preprint server for health sciences · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Clinical and genotypic analysis of 79 children with methylmalonic acidemia: a retrospective single-center study in China.Frontiers in endocrinology · 2026Article
- Vitamin B12 Alleviates Hepatic Ischemia-Reperfusion Injury with Restoration of Propanoate Metabolism and Mitochondrial Function.Journal of inflammation research · 2026Article
- Methylmalonate accumulation contributes to myocardial vulnerability post-reperfusion: a novel therapeutic target and prognostic biomarker.BMC medicine · 2025Article
- Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming.Nature communications · 2025Article
- Osmolytes vs. Anabolic Reserves: Contrasting Gonadal Metabolomes in Two Sympatric Mediterranean Sea Urchins.Metabolites · 2025Article
- Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.Molecular medicine (Cambridge, Mass.) · 2025Review
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27 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence of effective causal treatments. Here we employ multi-layered omics profiling combined with biochemical and clinical features of individuals with MMA to reveal a molecular diagnosis for 177 out of 210 (84%) cases, the majority (148) of whom display pathogenic variants in methylmalonyl-CoA mutase (MMUT). Stratification of these data layers by disease severity shows dysregulation of the tricarboxylic acid cycle and its replenishment (anaplerosis) by glutamine. The relevance of these disturbances is evidenced by multi-organ metabolomics of a hemizygous Mmut mouse model as well as through identification of physical interactions between MMUT and glutamine anaplerotic enzymes. Using stable-isotope tracing, we find that treatment with dimethyl-oxoglutarate restores deficient tricarboxylic acid cycling. Our work highlights glutamine anaplerosis as a potential therapeutic intervention point in MMA.
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