Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

PLoS One. 2016 Nov 18;11(11):e0166682. doi: 10.1371/journal.pone.0166682. eCollection 2016.


Background: We hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects.

Methods: Rat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed.

Results: GPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers.

Conclusion: GPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.

MeSH terms

  • Animals
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Glycerylphosphorylcholine / pharmacology*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / metabolism
  • NADPH Oxidases / metabolism
  • Nitric Oxide / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxygen Consumption
  • Rats
  • Reperfusion Injury / metabolism
  • Xanthine Dehydrogenase / metabolism


  • Nitric Oxide
  • Malondialdehyde
  • Glycerylphosphorylcholine
  • Xanthine Dehydrogenase
  • NADPH Oxidases
  • Glutathione
  • Glutathione Disulfide

Grants and funding

The study was supported by Hungarian Science Research Fund (OTKA) K104656, NKFI K120232 grants and GINOP-2.3.2-15-2016-00015. MB was the principle investigator, ET, and AG were associated researchers of the grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.