European Journal of Applied Physiology

, Volume 119, Issue 2, pp 315–331 | Cite as

Mitochondrial health and muscle plasticity after spinal cord injury

  • Ashraf S. GorgeyEmail author
  • Oksana Witt
  • Laura O’Brien
  • Christopher Cardozo
  • Qun Chen
  • Edward J. Lesnefsky
  • Zachary A. Graham
Invited Review


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.


Spinal cord injury Mitochondria Muscle atrophy Reactive oxygen species Peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 α) Androgens Neuromuscular electrical stimulation (NMES) Functional electrical stimulation (FES) Resistance training 



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).

Author 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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Spinal Cord Injury and DisordersHunter Holmes McGuire VA Medical CenterRichmondUSA
  2. 2.Department of Physiology and BiophysicsPauley Heart CenterRichmondUSA
  3. 3.Division of Cardiology, Department of MedicinePauley Heart CenterRichmondUSA
  4. 4.Medical ServicesHunter Holmes McGuire VA Medical CenterRichmondUSA
  5. 5.Department of Biochemistry and Molecular BiologyVirginia Commonwealth UniversityRichmondUSA
  6. 6.Department of Physical Medicine and RehabilitationVirginia Commonwealth UniversityRichmondUSA
  7. 7.Faculty of Physical TherapyCairo UniversityGizaEgypt
  8. 8.James J. Peters VA Medical CenterBronxUSA
  9. 9.Department of MedicineIcahn School of MedicineNew YorkUSA
  10. 10.Department of Rehabilitation MedicineIcahn School of MedicineNew YorkUSA
  11. 11.The Bone ProgramIcahn School of MedicineNew YorkUSA
  12. 12.Department of Veterans AffairsHunter Holmes McGuire Medical Center, Spinal Cord Injury and Disorders ServiceRichmondUSA

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