The Effect of Cellular Coenzyme Q 10 Deficiency on Lysosomal Acidification.

Coenzyme Q(10)(CoQ(10)) 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 CoQ(10)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 CoQ(10)deficiency on lysosomal acidification. In order to investigate this, a neuronal cell model of CoQ(10)deficiency was established via the treatment of SH-SY5Y cells with para-aminobenzoic acid (PABA). This method works through the competitive inhibition of the CoQ(10)biosynthetic pathway enzyme, CoQ(2). A single 1 mM (5 days) treatment with PABA resulted in a decrease of up to 58% in cellular CoQ(10)(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 CoQ(10)(5 mu M, 3 days) was able to restore cellular CoQ(10)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 CoQ(10)status and the possibility that a deficit in the status of this isoprenoid may result in an impairment of lysosomal acidification.