ArticleThe Journal of biological chemistry2009
Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 101 citations in OpenAlex.
- Preconditioning and Posttreatment Strategies in Neonatal Hypoxic-Ischemic Encephalopathy: Recent Advances and Clinical Challenges.Molecular neurobiology · 2025Review
- Aspartate in the Brain: A Review.Neurochemical research · 2025Review
- Fueling Brain Inhibition: Integrating GABAergic Neurotransmission and Energy Metabolism.Neurochemical research · 2025Review
- MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity.Scientific reports · 2025Article
- Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning.Journal of neurochemistry · 2024Article
- The Warburg effect: a signature of mitochondrial overload.Trends in cell biology · 2023Review
- Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver.Molecular genetics and metabolism reports · 2023Article
- Lactate shuttling as an allostatic means of thermoregulation in the brain.Frontiers in neuroscience · 2023Article
- Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders.Frontiers in neuroscience · 2023Review
- The NaeLife · 2022Article
- CaScience advances · 2022Article
- Saturation of the mitochondrial NADH shuttles drives aerobic glycolysis in proliferating cells.Molecular cell · 2022Article
- AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease.International journal of molecular sciences · 2022Review
- l-Aspartate: An Essential Metabolite for Plant Growth and Stress Acclimation.Molecules (Basel, Switzerland) · 2021Review
- The malate-aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway.IUBMB life · 2020Review
- NADSignal transduction and targeted therapy · 2020Review
- Calcium regulation of T cell metabolismCurrent opinion in physiology · 2020Article
- Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply.The Journal of biological chemistry · 2020Article
- The Response to Stimulation in Neurons and Astrocytes.Neurochemical research · 2019Review
- Glutamate-oxaloacetate transaminase activity promotes palmitate lipotoxicity in rat hepatocytes by enhancing anaplerosis and citric acid cycle flux.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca2+ signaling in mitochondria has been mainly attributed to Ca2+ entry to the matrix through the Ca2+ uniporter and activation of mitochondrial matrix dehydrogenases. However, mitochondria can also sense increases in cytosolic Ca2+ through a mechanism that involves the aspartate-glutamate carriers, extramitochondrial Ca2+ activation of the NADH malate-aspartate shuttle (MAS). Both pathways are linked through the shared substrate alpha-ketoglutarate (alphaKG). Here we have studied the interplay between the two pathways under conditions of Ca2+ activation. We show that alphaKG becomes limiting when Ca2+ enters in brain or heart mitochondria, but not liver mitochondria, resulting in a drop in alphaKG efflux through the oxoglutarate carrier and in a drop in MAS activity. Inhibition of alphaKG efflux and MAS activity by matrix Ca2+ in brain mitochondria was fully reversible upon Ca2+ efflux. Because of their differences in cytosolic calcium concentration requirements, the MAS and Ca2+ uniporter-mitochondrial dehydrogenase pathways are probably sequentially activated during a Ca2+ transient, and the inhibition of MAS at the center of the transient may provide an explanation for part of the increase in lactate observed in the stimulated brain in vivo.
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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.