The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification
Coenzyme Q<sub>10 </sub>(CoQ<sub>10</sub>) 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<sub>10 </sub>l...
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doaj-0330323067704bb59e55f7c3bad3db622020-11-25T03:20:05ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0191923192310.3390/jcm9061923The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal AcidificationRobert. A. Heaton0Simon Heales1Khalid Rahman2Darren. W. Sexton3Iain Hargreaves4School of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKNeurometabolic Unit, National Hospital, Queen Square, London WC1N 3BG, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKCoenzyme Q<sub>10 </sub>(CoQ<sub>10</sub>) 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<sub>10 </sub>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<sub>10 </sub>deficiency on lysosomal acidification. In order to investigate this, a neuronal cell model of CoQ<sub>10 </sub>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<sub>10</sub> biosynthetic pathway enzyme, CoQ<sub>2</sub>. A single 1 mM (5 days) treatment with PABA resulted in a decrease of up to 58% in cellular CoQ<sub>10</sub> (<i>p</i> < 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 (<i>p</i> < 0.05). It was found that subsequent treatment with CoQ<sub>10 </sub>(5 µM, 3 days) was able to restore cellular CoQ<sub>10</sub> concentration (<i>p</i> < 0.005), which was associated with an increase in fluorescence from both probes to around 90% of controls (<i>p</i> < 0.05), suggesting a restoration of lysosomal pH. This study provides insights into the association between lysosomal pH and cellular CoQ<sub>10 </sub>status and the possibility that a deficit in the status of this isoprenoid may result in an impairment of lysosomal acidification.https://www.mdpi.com/2077-0383/9/6/1923coenzyme Q<sub>10</sub>lysosomemitochondrialorganellescompetitive inhibitionlysosomal pH |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert. A. Heaton Simon Heales Khalid Rahman Darren. W. Sexton Iain Hargreaves |
spellingShingle |
Robert. A. Heaton Simon Heales Khalid Rahman Darren. W. Sexton Iain Hargreaves The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification Journal of Clinical Medicine coenzyme Q<sub>10</sub> lysosome mitochondrial organelles competitive inhibition lysosomal pH |
author_facet |
Robert. A. Heaton Simon Heales Khalid Rahman Darren. W. Sexton Iain Hargreaves |
author_sort |
Robert. A. Heaton |
title |
The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification |
title_short |
The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification |
title_full |
The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification |
title_fullStr |
The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification |
title_full_unstemmed |
The Effect of Cellular Coenzyme Q<sub>10</sub> Deficiency on Lysosomal Acidification |
title_sort |
effect of cellular coenzyme q<sub>10</sub> deficiency on lysosomal acidification |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-06-01 |
description |
Coenzyme Q<sub>10 </sub>(CoQ<sub>10</sub>) 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<sub>10 </sub>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<sub>10 </sub>deficiency on lysosomal acidification. In order to investigate this, a neuronal cell model of CoQ<sub>10 </sub>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<sub>10</sub> biosynthetic pathway enzyme, CoQ<sub>2</sub>. A single 1 mM (5 days) treatment with PABA resulted in a decrease of up to 58% in cellular CoQ<sub>10</sub> (<i>p</i> < 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 (<i>p</i> < 0.05). It was found that subsequent treatment with CoQ<sub>10 </sub>(5 µM, 3 days) was able to restore cellular CoQ<sub>10</sub> concentration (<i>p</i> < 0.005), which was associated with an increase in fluorescence from both probes to around 90% of controls (<i>p</i> < 0.05), suggesting a restoration of lysosomal pH. This study provides insights into the association between lysosomal pH and cellular CoQ<sub>10 </sub>status and the possibility that a deficit in the status of this isoprenoid may result in an impairment of lysosomal acidification. |
topic |
coenzyme Q<sub>10</sub> lysosome mitochondrial organelles competitive inhibition lysosomal pH |
url |
https://www.mdpi.com/2077-0383/9/6/1923 |
work_keys_str_mv |
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