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Heaton, R, Heales, S, Rahman, K, Sexton, DW and Hargreaves, IP (2020) The Effect of Cellular Coenzyme Q10 Deficiency on Lysosomal Acidification. Journal of Clinical Medicine, 9 (6). ISSN 2077-0383
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Abstract
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.
| Item Type: | Article |
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| Uncontrolled Keywords: | 1103 Clinical Sciences |
| Subjects: | Q Science > QD Chemistry |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | MDPI AG |
| Date Deposited: | 19 Jun 2020 15:05 |
| Last Modified: | 04 Sep 2021 07:08 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/13139 |
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