The Effect of Cellular Coenzyme Q₁₀ Deficiency on Lysosomal Acidification

Coenzyme Q₁₀ (CoQ₁₀) deficiency currently represents the only treatable mitochondrial disorder, however, little is known about how it may affect other organelles. The lysosome has been found to have a large concentration of CoQ₁₀ localised at its membrane; additionally, it has been suggested that it plays a role in the normal acidification of the lysosomal lumen. As a result, in this study we assessed the effect of CoQ₁₀ deficiency on lysosomal acidification. In order to investigate this, a neuronal cell model of CoQ₁₀ deficiency was established via the treatment of SH-SY5Y cells with para-aminobenzoic acid (PABA). This method works through the competitive inhibition of the CoQ₁₀ biosynthetic pathway enzyme, CoQ₂. A single 1 mM (5 days) treatment with PABA resulted in a decrease of up to 58% in cellular CoQ₁₀ (p < 0.05). It was found that this resulted in a significant decrease in fluorescence of both the LysoSensor (23%) and LysoTracker (35%) probes used to measure lysosomal pH (p < 0.05). It was found that subsequent treatment with CoQ₁₀ (5 µM, 3 days) was able to restore cellular CoQ₁₀ concentration (p < 0.005), which was associated with an increase in fluorescence from both probes to around 90% of controls (p < 0.05), suggesting a restoration of lysosomal pH. This study provides insights into the association between lysosomal pH and cellular CoQ₁₀ status and the possibility that a deficit in the status of this isoprenoid may result in an impairment of lysosomal acidification.