ArticleCell metabolism2018
Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations.
Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.Molecular medicine (Cambridge, Mass.) · 2020Pooled it
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- Mitochondrial DNA mutations are associated with impaired oxidative phosphorylation and enhanced imatinib response in chronic myeloid leukemia.HemaSphere · 2026Article
- Glutamine Metabolism in Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2026Review
- Polyunsaturated fatty acid sequestration protects against mitochondrial dysfunction-induced ferroptosis.EMBO reports · 2026Article
- Ampyrone is a direct agonist of human tyrosinase and a potential therapeutic for hypopigmentation disorders.JCI insight · 2026Article
- Renal glycosuria triggers a coordinated mannose and glutamine metabolic program to maintain glucose homeostasis.Cell reports · 2026Article
- Untargeted Metabolomics Analysis Reveals Potential Metabolic Targets in Gemcitabine-Treated Pancreatic Cancer Cells.Metabolites · 2026Article
- NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.Science advances · 2026Article
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Transcription Factor ATF4 Deletion Reprograms Glucose Metabolism in Clear Cell Renal Cell Carcinoma.Cancers · 2026Article
- SUCNR1 coordinates metabolic flux, mitochondrial function, and nutrient-dependent adaptation in hepatocytes.Science advances · 2026Article
- Lysosomes contribute to the synthesis of tricarboxylic acid-related metabolites in the hippocampus.Life metabolism · 2026Article
- Metabolic Reprogramming Coordinates Mannose and Glutamine Metabolism to Maintain Glucose Homeostasis During Glycosuria.bioRxiv : the preprint server for biology · 2026Article
- Comparative analysis of muscle pathologies and metabolic signaling in mouse models of mitochondrial dysfunction.Scientific reports · 2026Article
- Targeting mitochondrial deubiquitinase USP30 to induce mitophagy in heteroplasmic mitochondrial diseases.Pharmacological reports : PR · 2026Article
- Modifying muscle metabolic dysregulation in inclusion body myositis with pioglitazone: a single-arm trial.Nature communications · 2026Article
- A novel microprotein MUCP1 promotes colorectal cancer metabolic reprogramming by regulating mitochondrial succinate transport.Neoplasia (New York, N.Y.) · 2026Article
- Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance.BioMed (Basel, Switzerland) · 2026Article
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
72 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Using molecular, biochemical, and untargeted stable isotope tracing approaches, we identify a previously unappreciated glutamine-derived α-ketoglutarate (αKG) energy-generating anaplerotic flux to be critical in mitochondrial DNA (mtDNA) mutant cells that harbor human disease-associated oxidative phosphorylation defects. Stimulating this flux with αKG supplementation enables the survival of diverse mtDNA mutant cells under otherwise lethal obligatory oxidative conditions. Strikingly, we demonstrate that when residual mitochondrial respiration in mtDNA mutant cells exceeds 45% of control levels, αKG oxidative flux prevails over reductive carboxylation. Furthermore, in a mouse model of mitochondrial myopathy, we show that increased oxidative αKG flux in muscle arises from enhanced alanine synthesis and release into blood, concomitant with accelerated amino acid catabolism from protein breakdown. Importantly, in this mouse model of mitochondriopathy, muscle amino acid imbalance is normalized by αKG supplementation. Taken together, our findings provide a rationale for αKG supplementation as a therapeutic strategy for mitochondrial myopathies.
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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.