ArticleThe Journal of cell biology2017
Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 170 citations in OpenAlex.
- Prelimbic cortex-associated stress sensitisation and region-specific mitochondrial adaptations across preclinical approaches relevant to PTSD and depression.Neurobiology of stress · 2026Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- TruncatingbioRxiv : the preprint server for biology · 2026Article
- Inhibition of the mitochondrial pyruvate carrier attenuates the integrated stress response activation in a cellular model of Huntington's disease.Molecular and cellular biochemistry · 2026Article
- Pharmacological rescue of mitochondrial dysfunction, neurite degeneration, and premature death of ALS and AD iPSC-derived neurons.bioRxiv : the preprint server for biology · 2026Article
- The metabolic consequences of evoked spreading depolarization in brain slices.Scientific reports · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- 20-hydroxyecdysone promotes brain development via upregulating MMP2 expression during metamorphosis in Helicoverpa armigera.PLoS genetics · 2026Article
- Species-specific serine metabolism differentially controls natural killer cell functions.Nature metabolism · 2025Article
- Metabolic dynamics of human external urethral sphincter myoblast differentiation and the effects of tricarboxylic acid cycle inhibition.Scientific reports · 2025Article
- Review
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Two-point calibration protocol for the Förster Resonance Energy Transfer indicator Pyronic in neurons.Neurophotonics · 2025Article
- Mitochondrial Glutamine Metabolism Drives Epileptogenesis in Primary Hippocampal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- 13C tracing in synaptosomes reveals that SGLT2 inhibition with dapagliflozin prevents metabolic deficits in the 5X-FAD model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Article
- The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders.Molecular neurobiology · 2025Review
- Advancing mitochondrial therapeutics: Synthesis and pharmacological evaluation of pyrazole-based inhibitors targeting the mitochondrial pyruvate carrier.European journal of medicinal chemistry · 2025Article
- Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications.Biomolecules · 2025Review
- Derivation and Characterization of IsogenicCells · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death. Reductions in mitochondrial pyruvate uptake do not compromise cellular energy metabolism, suggesting neuronal metabolic flexibility. Rather, MPC inhibition rewires mitochondrial substrate metabolism to preferentially increase reliance on glutamate to fuel energetics and anaplerosis. Mobilizing the neuronal glutamate pool for oxidation decreases the quantity of glutamate released upon depolarization and, in turn, limits the positive-feedback cascade of excitotoxic neuronal injury. The finding links mitochondrial pyruvate metabolism to glutamatergic neurotransmission and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitotoxicity.
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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.