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Intertwined ROS and Metabolic Signaling at the Neuron-Astrocyte Interface

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Abstract

Metabolism and redox signalling share critical nodes in the nervous system. In the last years, a series of major findings have challenged the current vision on how neural reactive oxygen species (ROS) are produced and handled in the nervous system. Once regarded as deleterious by-products, ROS are now shown to be essential for a metabolic and redox crosstalk. In turn, this coupling defines neural viability and function to control behaviour or leading to neurodegeneration when compromised. Findings like a different assembly of mitochondrial respiratory supercomplexes in neurons and astrocytes stands behind a divergent production of ROS in either cell type, more prominent in astrocytes. ROS levels are however tightly controlled by an antioxidant machinery in astrocytes, assumed as more efficient than that of neurons, to regulate redox signalling. By exerting this control in ROS abundance, metabolic functions are finely tuned in both neural cells. Further, a higher engagement of mitochondrial respiration and oxidative function in neurons, underpinned by redox equivalents supplied from the pentose phosphate pathway and from glia, differs from the otherwise strong glycolytic capacity of astrocytes. Here, we recapitulate major findings on how ROS and metabolism differ between neural cells but merge to define reciprocal signalling pathways, ultimately defining neural function and fate.

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Acknowledgements

We are grateful to Prof. Juan P. Bolaños for his continuous support, mentoring and insightful scientific input. This publication is supported by funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 793987. Figures were modified from templates provided by Servier Medical Art.

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Authors and Affiliations

  1. Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain

    Carlos Vicente-Gutiérrez, Daniel Jiménez-Blasco & Rubén Quintana-Cabrera

  2. Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain

    Carlos Vicente-Gutiérrez, Daniel Jiménez-Blasco & Rubén Quintana-Cabrera

  3. Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain

    Daniel Jiménez-Blasco

  4. Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain

    Rubén Quintana-Cabrera

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  1. Carlos Vicente-Gutiérrez
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Correspondence to Rubén Quintana-Cabrera.

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Vicente-Gutiérrez, C., Jiménez-Blasco, D. & Quintana-Cabrera, R. Intertwined ROS and Metabolic Signaling at the Neuron-Astrocyte Interface. Neurochem Res 46, 23–33 (2021). https://doi.org/10.1007/s11064-020-02965-9

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