Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells LackingCOQ6 Article Swipe
Manuel J. Acosta Lopez
,
Eva Trevisson
,
Marcella Canton
,
Luis Vázquez-Fonseca
,
Valeria Morbidoni
,
Elisa Baschiera
,
Chiara Frasson
,
Ludovic Pélosi
,
Bérengère Rascalou
,
María Andrea Desbats
,
María Alcázar‐Fabra
,
José Julián Ríos
,
Alicia Sánchez‐García
,
Giuseppe Basso
,
Plácido Navas
,
Fabien Pierrel
,
Gloria Brea‐Calvo
,
Leonardo Salviati
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1155/2019/3904905
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1155/2019/3904905
Coenzyme Q (CoQ), a redox-active lipid, is comprised of a quinone group and a polyisoprenoid tail. It is an electron carrier in the mitochondrial respiratory chain, a cofactor of other mitochondrial dehydrogenases, and an essential antioxidant. CoQ requires a large set of enzymes for its biosynthesis; mutations in genes encoding these proteins cause primary CoQ deficiency, a clinically and genetically heterogeneous group of diseases. Patients with CoQ deficiency often respond to oral CoQ 10 supplementation. Treatment is however problematic because of the low bioavailability of CoQ 10 and the poor tissue delivery. In recent years, bypass therapy using analogues of the precursor of the aromatic ring of CoQ has been proposed as a promising alternative. We have previously shown using a yeast model that vanillic acid (VA) can bypass mutations of COQ6 , a monooxygenase required for the hydroxylation of the C5 carbon of the ring. In this work, we have generated a human cell line lacking functional COQ6 using CRISPR/Cas9 technology. We show that these cells cannot synthesize CoQ and display severe ATP deficiency. Treatment with VA can recover CoQ biosynthesis and ATP production. Moreover, these cells display increased ROS production, which is only partially corrected by exogenous CoQ, while VA restores ROS to normal levels. Furthermore, we show that these cells accumulate 3-decaprenyl-1,4-benzoquinone, suggesting that in mammals, the decarboxylation and C1 hydroxylation reactions occur before or independently of the C5 hydroxylation. Finally, we show that COQ6 isoform c (transcript NM_182480) does not encode an active enzyme. VA can be produced in the liver by the oxidation of vanillin, a nontoxic compound commonly used as a food additive, and crosses the blood-brain barrier. These characteristics make it a promising compound for the treatment of patients with CoQ deficiency due to COQ6 mutations.
Related Topics
Concepts
Coenzyme Q – cytochrome c reductase
Biochemistry
Mitochondrial respiratory chain
Hydroxylation
Biosynthesis
Cofactor
Biology
Mitochondrion
Enzyme
Mitochondrial disease
Gene
Cytochrome c
Mitochondrial DNA
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1155/2019/3904905
- http://downloads.hindawi.com/journals/omcl/2019/3904905.pdf
- OA Status
- hybrid
- Cited By
- 44
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2956709696
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2956709696Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1155/2019/3904905Digital Object Identifier
- Title
-
Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells LackingCOQ6Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-07-10Full publication date if available
- Authors
-
Manuel J. Acosta Lopez, Eva Trevisson, Marcella Canton, Luis Vázquez-Fonseca, Valeria Morbidoni, Elisa Baschiera, Chiara Frasson, Ludovic Pélosi, Bérengère Rascalou, María Andrea Desbats, María Alcázar‐Fabra, José Julián Ríos, Alicia Sánchez‐García, Giuseppe Basso, Plácido Navas, Fabien Pierrel, Gloria Brea‐Calvo, Leonardo SalviatiList of authors in order
- Landing page
-
https://doi.org/10.1155/2019/3904905Publisher landing page
- PDF URL
-
https://downloads.hindawi.com/journals/omcl/2019/3904905.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://downloads.hindawi.com/journals/omcl/2019/3904905.pdfDirect OA link when available
- Concepts
-
Coenzyme Q – cytochrome c reductase, Biochemistry, Mitochondrial respiratory chain, Hydroxylation, Biosynthesis, Cofactor, Biology, Mitochondrion, Enzyme, Mitochondrial disease, Gene, Cytochrome c, Mitochondrial DNATop concepts (fields/topics) attached by OpenAlex
- Cited by
-
44Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 7, 2023: 7, 2022: 8, 2021: 14Per-year citation counts (last 5 years)
- References (count)
-
36Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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