Skeletal Muscle Mitochondrial Physiology in Children With Cerebral Palsy: Considerations for Healthy Aging

Sudarshan Dayanidhi*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Skeletal muscle contractile proteins require a constant supply of energy to produce force needed for movement. Energy (ATP) is primarily produced by mitochondrial organelles, located within and around muscle fibers, by oxidative phosphorylation that couples electron flux through the electron transport chain to create a proton gradient across the inner mitochondrial membrane that is in turn used by the ATP synthase. Mitochondrial networks increase in size by biogenesis to increase mitochondrial abundance and activity in response to endurance exercise, while their function and content reduce with constant inactivity, such as during muscle atrophy. During healthy aging, there is an overall decline in mitochondrial activity and abundance, increase in mitochondrial DNA mutations, potential increase in oxidative stress, and reduction in overall muscular capacity. Many of these alterations can be attenuated by consistent endurance exercise. Children with cerebral palsy (CP) have significantly increased energetics of movement, reduced endurance capacity, and increased perceived effort. Recent work in leg muscles in ambulatory children with CP show a marked reduction in mitochondrial function. Arm muscles show that mitochondrial protein content and mitochondria DNA copy number are lower, suggesting a reduction in mitochondrial abundance, along with a reduction in markers for mitochondrial biogenesis. Gene expression networks are reduced for glycolytic and mitochondrial pathways and share similarities with gene networks with aging and chronic inactivity. Given the importance of mitochondria for energy production and changes with aging, future work needs to assess changes in mitochondria across the lifespan in people with CP and the effect of exercise on promoting metabolic health.

Original languageEnglish (US)
Article number735009
JournalFrontiers in Neurology
StatePublished - Sep 13 2021


  • cerebral palsy
  • energetics
  • mitochondria
  • oxidative phosphorylation
  • skeletal muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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