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Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate–Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism

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Abstract

The malate–aspartate NADH shuttle (MAS) operates in neurons and other cells to translocate reducing equivalents from the cytosol to the mitochondrial matrix, thus allowing a continued flux through the glycolytic pathway and metabolism of extracellular lactate. Recent discoveries have taught us that MAS is regulated by fluctuations in cytosolic Ca2+ levels, and that this regulation is required to maintain a tight coupling between neuronal activity and mitochondrial respiration and oxidative phosphorylation. At cytosolic Ca2+ fluctuations below the threshold of the mitochondrial calcium uniporter, there is a positive correlation between Ca2+ and MAS activity; however, if cytosolic Ca2+ increases above the threshold, MAS activity is thought to be reduced by an intricate mechanism. The latter forces the neurons to partly rely on anaerobic glycolysis producing lactate that may be metabolized subsequently, by neurons or other cells. In this review, we will discuss the evidence for Ca2+-mediated regulation of MAS that have been uncovered over the last decade or so, together with the need for further verification, and examine the metabolic ramifications for neurons.

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Authors and Affiliations

  1. Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28049, Madrid, Spain

    Jorgina Satrústegui

  2. Centro de Investigación Biomédica en Red de Enfermedades Raras, 28049, Madrid, Spain

    Jorgina Satrústegui

  3. Instituto de Investigación Sanitaria Fundación Jiménez Díaz, 28040, Madrid, Spain

    Jorgina Satrústegui

  4. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark

    Lasse K. Bak

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  1. Jorgina Satrústegui
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  2. Lasse K. Bak
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Correspondence to Jorgina Satrústegui.

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Special Issue: In honor of Dr. Gerald Dienel.

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Satrústegui, J., Bak, L.K. Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate–Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism. Neurochem Res 40, 2425–2430 (2015). https://doi.org/10.1007/s11064-015-1652-8

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  • DOI: https://doi.org/10.1007/s11064-015-1652-8

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