ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 113 citations in OpenAlex.
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- When calcium calls the shots in FAD-dependent respiration.Nature metabolism · 2026Article
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- Combined ketone body and glutamine supplementation restores aerobic energy production in AGC1-deficient neuronal progenitors.Cell death & disease · 2025Article
- Ceftriaxone alleviates mitochondrial damage through the inhibition of extrasynaptic NMDA receptor-mediated changes in intracellular calcium levels to improve cognitive deficits in APP/PS1 mice.Alzheimer's research & therapy · 2025Article
- Presynaptic ATP Decreases During Physiological-Like Activity in Neurons Tuned for High-Frequency Transmission.Journal of neurochemistry · 2025Article
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Mitochondrial Dysfunction as a Biomarker of Illness State in Bipolar Disorder: A Critical Review.Brain sciences · 2024Review
- The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions.Nature communications · 2024Article
- Ketone body β-hydroxybutyrate (BHB) preserves mitochondrial bioenergetics.Scientific reports · 2023Article
- Calcium-Dependent Interaction of Nitric Oxide Synthase with CytochromeBrain sciences · 2023Article
- Article
- Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy.Metabolites · 2023Review
- Mitochondrial responses to intracellular CaJournal of neurophysiology · 2023Article
- A CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.European review for medical and pharmacological sciences · 2022Review
- Mitochondrial HAnnual review of physiology · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport through the Ca2+ uniporter. We have studied the role of Ca2+ signaling in the regulation of mitochondrial respiration in intact mouse cortical neurons in basal conditions and in response to increased workload caused by increases in [Na+]cyt (veratridine, high-K+ depolarization) and/or [Ca2+]cyt (carbachol). Respiration in nonstimulated neurons on 2.5-5 mm glucose depends on ARALAR-malate aspartate shuttle (MAS), with a 46% drop in aralar KO neurons. All stimulation conditions induced increased OCR (oxygen consumption rate) in the presence of Ca2+, which was prevented by BAPTA-AM loading (to preserve the workload), or in Ca2+-free medium (which also lowers cell workload). SCaMC-3 limits respiration only in response to high workloads and robust Ca2+ signals. In every condition tested Ca2+ activation of ARALAR-MAS was required to fully stimulate coupled respiration by promoting pyruvate entry into mitochondria. In aralar KO neurons, respiration was stimulated by veratridine, but not by KCl or carbachol, indicating that the Ca2+ uniporter pathway played a role in the first, but not in the second condition, even though KCl caused an increase in [Ca2+]mit. The results suggest a requirement for ARALAR-MAS in priming pyruvate entry in mitochondria as a step needed to activate respiration by Ca2+ in response to moderate workloads.
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