Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

Overview

Journal Antioxidants (Basel)

Date 2023 Jul 29

PMID 37508007

Authors

Carmine Staiano

Laura Garcia-Corzo

David Mantle

Nadia Turton

Lauren E Millichap

Gloria Brea-Calvo

Iain Hargreaves

Affiliations

Soon will be listed here.

Abstract

Originally identified as a key component of the mitochondrial respiratory chain, Coenzyme Q (CoQ or CoQ for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane types. Cells rely on endogenous CoQ biosynthesis, and defects in this still-not-completely understood pathway result in primary CoQ deficiencies, a group of conditions biochemically characterised by decreased tissue CoQ levels, which in turn are linked to functional defects. Secondary CoQ deficiencies may result from a wide variety of cellular dysfunctions not directly linked to primary synthesis. In this article, we review the current knowledge on CoQ biosynthesis, the defects leading to diminished CoQ levels in human tissues and their associated clinical manifestations.

Citing Articles

FgUbiH Is Essential for Vegetative Development, Energy Metabolism, and Antioxidant Activity in .

Ge J, Zhai H, Tang L, Zhang S, Lv Y, Ma P Microorganisms. 2024; 12(10).

PMID: 39458403 PMC: 11509934. DOI: 10.3390/microorganisms12102093.

Research Progress of Coenzyme Q in Diabetes Mellitus and Its Common Complications.

Xia J, Li X, Bai C, Han X Diabetes Metab Syndr Obes. 2024; 17:3629-3641.

PMID: 39376660 PMC: 11457790. DOI: 10.2147/DMSO.S481690.

Homozygous variant in COQ7 causes autosomal recessive hereditary spastic paraplegia.

Qiu Y, Xiong Y, Wang L, Zhu M, Tan D, Hong D Ann Clin Transl Neurol. 2024; 11(4):1067-1074.

PMID: 38439593 PMC: 11021622. DOI: 10.1002/acn3.52037.

CoQ and Mitochondrial Dysfunction in Alzheimer's Disease.

Fisar Z, Hroudova J Antioxidants (Basel). 2024; 13(2).

PMID: 38397789 PMC: 10885987. DOI: 10.3390/antiox13020191.

References

Banerjee R, Purhonen J, Kallijarvi J . The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology. FEBS J. 2021; 289(22):6936-6958. DOI: 10.1111/febs.16164. View

Olgac A, Oztoprak U, Kasapkara C, Kilic M, Yuksel D, Derinkuyu E . A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation. J Pediatr Endocrinol Metab. 2019; 33(1):165-170. DOI: 10.1515/jpem-2019-0245. View

Gonzalez-Garcia P, Diaz-Casado M, Hidalgo-Gutierrez A, Jimenez-Sanchez L, Bakkali M, Barriocanal-Casado E . The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency. Redox Biol. 2022; 55:102403. PMC: 9301574. DOI: 10.1016/j.redox.2022.102403. View

Kuhl I, Miranda M, Atanassov I, Kuznetsova I, Hinze Y, Mourier A . Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals. Elife. 2017; 6. PMC: 5703644. DOI: 10.7554/eLife.30952. View

Tsui H, Pham N, Amer B, Bradley M, Gosschalk J, Gallagher-Jones M . Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. J Lipid Res. 2019; 60(7):1293-1310. PMC: 6602128. DOI: 10.1194/jlr.M093534. View

Emekli-Alturfan E, Alturfan A . The emerging relationship between vitamin K and neurodegenerative diseases: a review of current evidence. Mol Biol Rep. 2022; 50(1):815-828. DOI: 10.1007/s11033-022-07925-w. View

Kelekci S, Evliyaoglu O, Sen V, Yolbas I, Uluca U, Tan I . The relationships between clinical outcome and the levels of total antioxidant capacity (TAC) and coenzyme Q (CoQ 10) in children with pandemic influenza (H 1 N1) and seasonal flu. Eur Rev Med Pharmacol Sci. 2012; 16(8):1033-8. View

Muthukumaran K, Leahy S, Harrison K, Sikorska M, Sandhu J, Cohen J . Orally delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson's disease. BMC Neurosci. 2014; 15:21. PMC: 3917573. DOI: 10.1186/1471-2202-15-21. View

Chase M, Cocchi M, Liu X, Andersen L, Holmberg M, Donnino M . Coenzyme Q10 in acute influenza. Influenza Other Respir Viruses. 2018; 13(1):64-70. PMC: 6304320. DOI: 10.1111/irv.12608. View

10.

Vo C, Michaud J, Elsen S, Faivre B, Bouveret E, Barras F . The O-independent pathway of ubiquinone biosynthesis is essential for denitrification in . J Biol Chem. 2020; 295(27):9021-9032. PMC: 7335794. DOI: 10.1074/jbc.RA120.013748. View

11.

Hargreaves I, Lane A, Sleiman P . The coenzyme Q10 status of the brain regions of Parkinson's disease patients. Neurosci Lett. 2008; 447(1):17-9. DOI: 10.1016/j.neulet.2008.09.069. View

12.

Teive H, Moro A, Moscovich M, Arruda W, Munhoz R . Statin-associated cerebellar ataxia. A Brazilian case series. Parkinsonism Relat Disord. 2016; 25:97-9. DOI: 10.1016/j.parkreldis.2016.02.005. View

13.

Granata C, Caruana N, Botella J, Jamnick N, Huynh K, Kuang J . High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content. Nat Commun. 2021; 12(1):7056. PMC: 8642543. DOI: 10.1038/s41467-021-27153-3. View

14.

Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C . Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid. J Med Genet. 2015; 52(11):779-83. PMC: 4680133. DOI: 10.1136/jmedgenet-2015-102986. View

15.

Lapointe C, Stefely J, Jochem A, Hutchins P, Wilson G, Kwiecien N . Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis. Cell Syst. 2017; 6(1):125-135.e6. PMC: 5799006. DOI: 10.1016/j.cels.2017.11.012. View

16.

Mugoni V, Postel R, Catanzaro V, De Luca E, Turco E, Digilio G . Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell. 2013; 152(3):504-18. PMC: 3574195. DOI: 10.1016/j.cell.2013.01.013. View

17.

Folkers K, Vadhanavikit S, Mortensen S . Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985; 82(3):901-4. PMC: 397155. DOI: 10.1073/pnas.82.3.901. View

18.

Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A . Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest. 2007; 117(3):765-72. PMC: 1804361. DOI: 10.1172/JCI29089. View

19.

Naini A, Lewis V, Hirano M, DiMauro S . Primary coenzyme Q10 deficiency and the brain. Biofactors. 2003; 18(1-4):145-52. DOI: 10.1002/biof.5520180217. View

20.

Lawrence J, Cox G, Gibson F . Biosynthesis of ubiquinone in Escherichia coli K-12: biochemical and genetic characterization of a mutant unable to convert chorismate into 4-hydroxybenzoate. J Bacteriol. 1974; 118(1):41-5. PMC: 246637. DOI: 10.1128/jb.118.1.41-45.1974. View