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Mitochondrial health and muscle plasticity after spinal cord injury

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Abstract

Mitochondria are responsible for aerobic respiration and large-scale ATP production in almost all cells of the body. Their function is decreased in many neurodegenerative and cardiovascular disease states, in metabolic disorders such as type II diabetes and obesity, and as a normal component of aging. Disuse of skeletal muscle from immobilization or unloading triggers alterations of mitochondrial density and activity. Resultant mitochondrial dysfunction after paralysis, which precedes muscle atrophy, may augment subsequent release of reactive oxygen species leading to protein ubiquitination and degradation. Spinal cord injury is a unique form of disuse atrophy as there is a complete or partial disruption in tonic communication between the central nervous system (CNS) and skeletal muscle. Paralysis, unloading and disruption of CNS communication result in a rapid decline in skeletal muscle function and metabolic status with disruption in activity of peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha and calcineurin, key regulators of mitochondrial health and function. External interventions, both acute and chronical with training using body-weight-assisted treadmill training or electrical stimulation have consistently demonstrated adaptations in skeletal muscle mitochondria, and expression of the genes and proteins required for mitochondrial oxidation of fats and carbohydrates to ATP, water, and carbon dioxide. The purpose of this mini-review is to highlight our current understanding as to how paralysis mechanistically triggers downstream regulation in mitochondrial density and activity and to discuss how mitochondrial dysfunction may contribute to skeletal muscle atrophy.

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Acknowledgements

The work is supported by the Department of Veteran Affairs, Veteran Health Administration, Rehabilitation Research and Development Service (B7867-W and B-2020-C) and DoD-CDRMP (W81XWH-14-SCIRP-CTA).

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Authors and Affiliations

  1. Spinal Cord Injury and Disorders, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Ashraf S. Gorgey

  2. Department of Physiology and Biophysics, Pauley Heart Center, Richmond, VA, USA

    Laura O’Brien & Edward J. Lesnefsky

  3. Division of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA, USA

    Qun Chen & Edward J. Lesnefsky

  4. Medical Services, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Edward J. Lesnefsky

  5. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA

    Edward J. Lesnefsky

  6. Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA

    Ashraf S. Gorgey & Oksana Witt

  7. Faculty of Physical Therapy, Cairo University, Giza, Egypt

    Ashraf S. Gorgey

  8. James J. Peters VA Medical Center, Bronx, NY, USA

    Christopher Cardozo & Zachary A. Graham

  9. Department of Medicine, Icahn School of Medicine, New York, NY, USA

    Christopher Cardozo & Zachary A. Graham

  10. Department of Rehabilitation Medicine, Icahn School of Medicine, New York, NY, USA

    Christopher Cardozo

  11. The Bone Program, Icahn School of Medicine, New York, NY, USA

    Christopher Cardozo

  12. Department of Veterans Affairs, Hunter Holmes McGuire Medical Center, Spinal Cord Injury and Disorders Service, 1201 Broad Rock Boulevard, Richmond, VA, 23249, USA

    Ashraf S. Gorgey

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  1. Ashraf S. Gorgey
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  2. Oksana Witt
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  4. Christopher Cardozo
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  5. Qun Chen
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  6. Edward J. Lesnefsky
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  7. Zachary A. Graham
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Contributions

ASG: provided funding support, developed the research hypothesis, submitted initial proposal, reviewed scientific evidence, helped writing and editing, and approved the final version. OW: reviewed scientific writing, summarized research finding, helped writing and editing, and approved the final version. LO’B: provided support for scientific writing, developed figures, helped editing and approved the final version. CC: provided critical feedback, assisted in scientific writing, helped editing, organizing and approved the final version. QC: provided support for scientific writing, developed figures, helped editing and approved the final version. EJL: provided critical feedback, assisted in scientific writing, helped editing, and approved the final version. ZAG: provided critical feedback, assisted in scientific writing, helped editing, organizing and approved the final version.

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Correspondence to Ashraf S. Gorgey.

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Communicated by Michael Lindinger.

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Gorgey, A.S., Witt, O., O’Brien, L. et al. Mitochondrial health and muscle plasticity after spinal cord injury. Eur J Appl Physiol 119, 315–331 (2019). https://doi.org/10.1007/s00421-018-4039-0

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