Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency.

Abstract

Coenzyme Q10 (CoQ10) deficiency (MIM 607426) causes a mitochondrial syndrome with variability in the clinical presentations. Patients with CoQ10 deficiency show inconsistent responses to oral ubiquinone-10 supplementation, with the highest percentage of unsuccessful results in patients with neurological symptoms (encephalopathy, cerebellar ataxia or multisystemic disease). Failure in the ubiquinone-10 treatment may be the result of its poor absorption and bioavailability, which may be improved by using different pharmacological formulations. In a mouse model (Coq9(X/X)) of mitochondrial encephalopathy due to CoQ deficiency, we have evaluated oral supplementation with water-soluble formulations of reduced (ubiquinol-10) and oxidized (ubiquinone-10) forms of CoQ10. Our results show that CoQ10 was increased in all tissues after supplementation with ubiquinone-10 or ubiquinol-10, with the tissue levels of CoQ10 with ubiquinol-10 being higher than with ubiquinone-10. Moreover, only ubiquinol-10 was able to increase the levels of CoQ10 in mitochondria from cerebrum of Coq9(X/X) mice. Consequently, ubiquinol-10 was more efficient than ubiquinone-10 in increasing the animal body weight and CoQ-dependent respiratory chain complex activities, and reducing the vacuolization, astrogliosis and oxidative damage in diencephalon, septum-striatum and, to a lesser extent, in brainstem. These results suggest that water-soluble formulations of ubiquinol-10 may improve the efficacy of CoQ10 therapy in primary and secondary CoQ10 deficiencies, other mitochondrial diseases and neurodegenerative diseases.

• Authors: Laura García-Corzo, Marta Luna-Sánchez, Carolina Doerrier, Francisco Ortiz, Germaine Escames, Darío Acuña-Castroviejo, Luis C López
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1842 Issue 7 Pg. 893-901 (Jul 2014) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24576561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Ubiquinone
• ubiquinol-10
• Ubiquinone Q2

Topics

• Animals
• Ataxia (drug therapy)
• Brain Diseases (drug therapy)
• Brain Stem (drug effects)
• Corpus Striatum (drug effects)
• Electron Transport (drug effects)
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects)
• Mitochondrial Diseases (drug therapy)
• Mitochondrial Encephalomyopathies (drug therapy)
• Muscle Weakness (drug therapy)
• Oxidative Stress (drug effects)
• Ubiquinone (analogs & derivatives, deficiency, pharmacology)