A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options
Coenzyme Q10 (CoQ10) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ10 is synthesized by all cells and defects in the synthesis pathway result in primary CoQ10 deficiency that frequently leads to severe mitochondrial disease syndrome. CoQ10 is exce...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426922000374 |
| _version_ | 1818205880003330048 |
|---|---|
| author | Ying Wang Evren Gumus Siegfried Hekimi |
| author_facet | Ying Wang Evren Gumus Siegfried Hekimi |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Coenzyme Q10 (CoQ10) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ10 is synthesized by all cells and defects in the synthesis pathway result in primary CoQ10 deficiency that frequently leads to severe mitochondrial disease syndrome. CoQ10 is exceedingly hydrophobic, insoluble, and poorly bioavailable, with the result that dietary CoQ10 supplementation produces no or only minimal relief for patients. We studied a patient from Turkey and identified and characterized a new mutation in the CoQ10 biosynthetic gene COQ7 (c.161G > A; p.Arg54Gln). We find that unexpected neuromuscular pathology can accompany CoQ10 deficiency caused by a COQ7 mutation. We also show that by-passing the need for COQ7 by providing the unnatural precursor 2,4-dihydroxybenzoic acid, as has been proposed, is unlikely to be an effective and safe therapeutic option. In contrast, we show for the first time in human patient cells that the respiratory defect resulting from CoQ10 deficiency is rescued by providing CoQ10 formulated with caspofungin (CF/CoQ). Caspofungin is a clinically approved intravenous fungicide whose surfactant properties lead to CoQ10 micellization, complete water solubilization, and efficient uptake by cells and organs in animal studies. These findings reinforce the possibility of using CF/CoQ in the clinical treatment of CoQ10-deficient patients. |
| first_indexed | 2024-12-12T04:04:09Z |
| format | Article |
| id | doaj.art-9ee5763dfc5b40acb3fbac7f38fb3a10 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-12T04:04:09Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-9ee5763dfc5b40acb3fbac7f38fb3a102022-12-22T00:38:49ZengElsevierMolecular Genetics and Metabolism Reports2214-42692022-06-0131100877A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment optionsYing Wang0Evren Gumus1Siegfried Hekimi2Department of Biology, McGill University, Montreal, Quebec, CanadaDepartment of Medical Genetics, Mugla Sitki Kocman University, TurkeyDepartment of Biology, McGill University, Montreal, Quebec, Canada; Corresponding author.Coenzyme Q10 (CoQ10) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ10 is synthesized by all cells and defects in the synthesis pathway result in primary CoQ10 deficiency that frequently leads to severe mitochondrial disease syndrome. CoQ10 is exceedingly hydrophobic, insoluble, and poorly bioavailable, with the result that dietary CoQ10 supplementation produces no or only minimal relief for patients. We studied a patient from Turkey and identified and characterized a new mutation in the CoQ10 biosynthetic gene COQ7 (c.161G > A; p.Arg54Gln). We find that unexpected neuromuscular pathology can accompany CoQ10 deficiency caused by a COQ7 mutation. We also show that by-passing the need for COQ7 by providing the unnatural precursor 2,4-dihydroxybenzoic acid, as has been proposed, is unlikely to be an effective and safe therapeutic option. In contrast, we show for the first time in human patient cells that the respiratory defect resulting from CoQ10 deficiency is rescued by providing CoQ10 formulated with caspofungin (CF/CoQ). Caspofungin is a clinically approved intravenous fungicide whose surfactant properties lead to CoQ10 micellization, complete water solubilization, and efficient uptake by cells and organs in animal studies. These findings reinforce the possibility of using CF/CoQ in the clinical treatment of CoQ10-deficient patients.http://www.sciencedirect.com/science/article/pii/S2214426922000374Coenzyme QCoQ10UbiquinoneCOQ7CoQ deficiency2,4-dihydroxybenzoic acid |
| spellingShingle | Ying Wang Evren Gumus Siegfried Hekimi A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options Molecular Genetics and Metabolism Reports Coenzyme Q CoQ10 Ubiquinone COQ7 CoQ deficiency 2,4-dihydroxybenzoic acid |
| title | A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options |
| title_full | A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options |
| title_fullStr | A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options |
| title_full_unstemmed | A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options |
| title_short | A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options |
| title_sort | novel coq7 mutation causing primarily neuromuscular pathology and its treatment options |
| topic | Coenzyme Q CoQ10 Ubiquinone COQ7 CoQ deficiency 2,4-dihydroxybenzoic acid |
| url | http://www.sciencedirect.com/science/article/pii/S2214426922000374 |
| work_keys_str_mv | AT yingwang anovelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions AT evrengumus anovelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions AT siegfriedhekimi anovelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions AT yingwang novelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions AT evrengumus novelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions AT siegfriedhekimi novelcoq7mutationcausingprimarilyneuromuscularpathologyanditstreatmentoptions |