Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction

Sci Rep. 2017 Apr 21;7(1):1003. doi: 10.1038/s41598-017-01149-w.


Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients' brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / diet therapy
  • Brain Injuries, Traumatic / metabolism
  • Brain Injuries, Traumatic / physiopathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dietary Supplements
  • Energy Metabolism / drug effects*
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Models, Biological
  • Neuroglia / cytology*
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Rotenone / adverse effects*
  • Spinal Cord Injuries / diet therapy
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology
  • Succinic Acid / pharmacology*


  • Rotenone
  • Succinic Acid