Biochemical Assessment of Coenzyme Q10 Deficiency

Abstract

Coenzyme Q₁₀ (CoQ₁₀) deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ₁₀ biosynthesis. Mutations in any of these genes are responsible for the primary CoQ₁₀ deficiency, but there are also different conditions that induce secondary CoQ₁₀ deficiency including mitochondrial DNA (mtDNA) depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ₁₀ deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ₁₀ supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ₁₀ content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ₁₀ biosynthesis rate using labeled precursors.

Keywords: CoQ10 biosynthesis; CoQ10 deficiency syndrome; coenzyme Q10; mitochondria diseases.

Figure 1

HPLC elution profile of lipid extracts from human skeletal muscular tissue. Patient pathological profile (red plot) shows that CoQ₁₀ is clearly diminished compared to healthy control volunteers (black plot). CoQ₉ is used as internal standard for normalization.

Figure 2

HPLC elution profile of lipid extracts from human fibroblasts cultured with the radiolabeled precursor ¹⁴C-p-HB. Patient pathological profile (red plot) shows that CoQ₁₀ is clearly diminished compared to control cells from healthy humans (blue plot). Left Y-axis shows the radio-flow detector scale (volts). Right Y-axis shows the UV-detector scale (absorbance units) for a standard pool of CoQ₁₀ and CoQ₉ (black plot). Notice that the only peak detected in this analysis corresponded with CoQ₁₀.