The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
The regulation of neuronal mitochondrial metabolism by calcium
Open accessAbstract
Calcium signalling is fundamental to the function of the nervous system, in association with changes in ionic gradients across the membrane. Although restoring ionic gradients is energetically costly, a rise in intracellular Ca 2+ acts through multiple pathways to increase ATP synthesis, matching energy supply to demand. Increasing cytosolic Ca 2+ stimulates metabolite transfer across the inner mitochondrial membrane through activation of Ca 2+‐regulated mitochondrial carriers, whereas an increase in matrix Ca 2+ stimulates the citric acid cycle and ATP synthase. The aspartate–glutamate exchanger Aralar/AGC1 (Slc25a12), a component of the malate–aspartate shuttle (MAS), is stimulated by modest increases in cytosolic Ca 2+ and upregulates respiration in cortical neurons by enhancing pyruvate supply into mitochondria. Failure to increase respiration in response to small (carbachol) and moderate (K+‐depolarization) workloads and blunted stimulation of respiration in response to high workloads (veratridine) in Aralar/AGC1 knockout neurons reflect impaired MAS activity and limited mitochondrial pyruvate supply. In response to large workloads (veratridine), acute stimulation of respiration occurs in the absence of MAS through Ca 2+ influx through the mitochondrial calcium uniporter (MCU) and a rise in matrix [Ca 2+]. Although the physiological importance of the MCU complex in work‐induced stimulation of respiration of CNS neurons is not yet clarified, abnormal mitochondrial Ca 2+ signalling causes pathology. Indeed, loss of function mutations in MICU1, a regulator of MCU complex, are associated with neuromuscular disease. In patient‐derived MICU1 deficient fibroblasts, resting matrix Ca 2+ is increased and mitochondria fragmented. Thus, the fine tuning of Ca 2+ signals plays a key role in shaping mitochondrial bioenergetics.
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Citations
Cites
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Brain Glucose Metabolism: Integration of Energetics with Function
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Mitochondria at the neuronal presynapse in health and disease
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Calcium, mitochondria and cell metabolism: A functional triangle in bioenergetics
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Energy matters: presynaptic metabolism and the maintenance of synaptic transmission
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The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions
Pilchova, I., Klacanova, K., Tatarkova, Z., Kaplan, P., & Racay, P. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6797460 · Cited by 198
Metadata
- Authors
- Llorente‐Folch, I., Rueda, C. B., Pardo, B., Szabadkai, G., Duchen, M. R., & Satrustegui, J.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2015-08-14
- Volume
- 593
- Issue
- 16
- Pages
- 3447-3462
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W1995237666
- Cited by
- 165
- References
- 14
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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