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Mitochondrial function in spinal cord injury and regeneration

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Abstract

Many people around the world suffer from some form of paralysis caused by spinal cord injury (SCI), which has an impact on quality and life expectancy. The spinal cord is part of the central nervous system (CNS), which in mammals is unable to regenerate, and to date, there is a lack of full functional recovery therapies for SCI. These injuries start with a rapid and mechanical insult, followed by a secondary phase leading progressively to greater damage. This secondary phase can be potentially modifiable through targeted therapies. The growing literature, derived from mammalian and regenerative model studies, supports a leading role for mitochondria in every cellular response after SCI: mitochondrial dysfunction is the common event of different triggers leading to cell death, cellular metabolism regulates the immune response, mitochondrial number and localization correlate with axon regenerative capacity, while mitochondrial abundance and substrate utilization regulate neural stem progenitor cells self-renewal and differentiation. Herein, we present a comprehensive review of the cellular responses during the secondary phase of SCI, the mitochondrial contribution to each of them, as well as evidence of mitochondrial involvement in spinal cord regeneration, suggesting that a more in-depth study of mitochondrial function and regulation is needed to identify potential targets for SCI therapeutic intervention.

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Acknowledgements

Special thanks to Fernando Faunes and Sol Torruella for critical reading of the manuscript.

Funding

This work was funded by FONDECYT 3190820 for PGS, 1180429 for JL and 1191770 for VE.

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Authors and Affiliations

  1. Center for Aging and Regeneration, Departamento de Biología Celular Y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, 8331150, Santiago, Chile

    Paula G. Slater, Miguel E. Domínguez-Romero, Maximiliano Villarreal, Verónica Eisner & Juan Larraín

  2. Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, 8331150, Santiago, Chile

    Verónica Eisner

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  2. Miguel E. Domínguez-Romero
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  3. Maximiliano Villarreal
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  4. Verónica Eisner
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PGS manuscript conceptualization and design, manuscript writing and editing, figure design and editing, and funding acquisition. MED-R manuscript writing, figure design and generation. MV manuscript writing. VE manuscript critical reading and editing. JL manuscript critical reading and editing, and funding acquisition.

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Correspondence to Paula G. Slater.

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Slater, P.G., Domínguez-Romero, M.E., Villarreal, M. et al. Mitochondrial function in spinal cord injury and regeneration. Cell. Mol. Life Sci. 79, 239 (2022). https://doi.org/10.1007/s00018-022-04261-x

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  • DOI: https://doi.org/10.1007/s00018-022-04261-x

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