COQ6 hydroxylates DHB

Stable Identifier
R-HSA-2162187
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
DHB is hydroxylated to DHDB by COQ6
ReviewStatus
5/5
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Flavin-dependent monooxygenase COQ6 (Heeringa et al. 2011) catalyses the C5-hydroxylation of 3-decaprenyl-4-hydroxybenzoic acid (DHB) to 3,4-dihydroxy-5-decaprenylbenzoic acid (DHDB). The electrons needed likely come from the iron-sulfur cluster on a ferredoxin that is recycled with NADPH (Nicoll et al., 2024; Gonzalez et al., 2023). COQ6 is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane (Gin et al. 2003). This reaction involving COQ6 was first confirmed in yeast, where hexaprenyl sidechains occur instead of decaprenyl moieties in human (Ozeir et al. 2011, Gin et al. 2003). In mammals, the decarboxylation and C1 hydroxylation reactions occur before or independently of the C5 hydroxylation (Acosta Lopez et al., 2019). Implication of a ferredoxin-ferredoxin reductase system to reduce COQ6 was initially proposed in yeast (Ozeir et al, 2011) and was validated in vitro with the resurrected tetrapod ancestral proteins COQ6, FDX2 and FDXR (Nicoll et al., 2024). This reaction involving COQ6 was first confirmed in yeast, where hexaprenyl sidechains occur instead of decaprenyl moieties in human (Ozeir et al. 2011, Gin et al. 2003).
Literature References
PubMed ID Title Journal Year
21944752 Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and substrate analogs rescue Coq6 deficiency

Ozeir, M, Fontecave, M, Lill, R, Pierrel, F, Webert, H, Mühlenhoff, U

Chem Biol 2011
31379988 Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells Lacking COQ6

Pelosi, L, Salviati, L, Trevisson, E, Basso, G, Desbats, MA, Pierrel, F, Vázquez-Fonseca, L, Alcázar-Fabra, M, Brea-Calvo, G, Ríos, JJ, Rascalou, B, Frasson, C, Navas, P, Acosta Lopez, MJ, Sánchez-García, A, Baschiera, E, Morbidoni, V, Canton, M

Oxid Med Cell Longev 2019
21540551 COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness

Nürnberg, P, Prokisch, H, Becker, C, Bakkaloglu, A, Killen, PD, Berdeli, A, McLaughlin, HM, Casarin, A, Varpizen, S, Zenker, M, Müller, D, Topaloglu, R, Airik, R, Krick, S, Raphael, Y, Zhou, W, Faul, C, Clarke, CF, Vega-Warner, V, Vlangos, CN, Wiggins, RC, Navas, P, Xie, LX, Gbadegesin, R, Ji, Z, Pertegato, V, Heeringa, SF, Trevisson, E, Mir, S, Doimo, M, Akman, S, Schoeb, DS, Reiser, J, Sloan, AJ, Salviati, L, Ovunc, B, Nürnberg, G, Mundel, P, Chernin, G, Kispert, A, Soliman, NA, Beissert, A, Rötig, A, Wang, S, Hildebrandt, F, Giorgi, G, Hurd, TW, Ashraf, S, Ozaltin, F, Santos-Ocaña, C, Hinkes, B, Bakkaloglu, SA, Kusakabe, T, Chaki, M, Saisawat, P, Matejas, V

J Clin Invest 2011
37476682 Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature

Nejad Biglari, H, Irilouzadian, R, Sarmadian, R, Hojabri, M, Gilani, A

Clin Med Insights Case Rep 2023
24270420 ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption

Salviati, L, Washburn, J, Choi, M, Barua, M, Gee, HY, Han, Z, Saleem, MA, Gok, F, Clarke, CF, Vega-Warner, V, Allen, SJ, Evans, J, Esteve-Rudd, J, Lifton, RP, Nitschké, P, El Desoky, S, Bole-Feysot, C, Levy, S, Airik, R, Ashraf, S, Pei, Y, Haberberger, B, Bierzynska, A, Woerner, S, Paterson, AD, Xie, LX, Bockenhauer, D, Antignac, C, Al-Hamed, MH, Hacihamdioglu, DO, Cochat, P, Kleta, R, Lovric, S, Pollak, M, Wiggins, RC, Avila-Casado, C, Cattran, DC, Zhou, W, Williams, DS, Hildebrandt, F, Prokisch, H, Kari, JA, Otto, EA, Song, X, Fang, H

J Clin Invest 2013
36843884 Clinical features and gene variation analysis of COQ8B nephropathy: Report of seven cases

Yang, Q, Zhang, Y, Liang, R, Chen, H, Yang, H, Wu, D, Law, CF, Yu, S, Zhang, G, Wang, A, Wang, M, Jiao, J, Chen, X

Front Pediatr 2022
38141230 Activation of Coq6p, a FAD Monooxygenase Involved in Coenzyme Q Biosynthesis, by Adrenodoxin Reductase/Ferredoxin

Hamdane, D, Chau-Duy Tam Vo, S, Lombard, M, Pierrel, F, Faivre, B, Gonzalez, L, Fontecave, M

Chembiochem 2024
12721307 The Saccharomyces cerevisiae COQ6 gene encodes a mitochondrial flavin-dependent monooxygenase required for coenzyme Q biosynthesis

Tzagoloff, A, Rothman, SC, Jonassen, T, Hsu, AY, Gin, P, Lee, PT, Clarke, CF

J Biol Chem 2003
27499296 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

Stefely, JA, Taylor, RW, Dolan, BK, Westphall, MS, Wilkerson, EM, Veling, MT, Wrobel, RL, Kim, JP, Jochem, A, Cho, H, Coon, JJ, Xia, C, Ulbrich, A, Gromek, KA, Rensvold, JW, Bohl, SL, Beebe, ET, Pagliarini, DJ, Werner, KM, Alston, CL, Floyd, BJ, Prokisch, H, Kremer, LS, Minogue, CE

Mol Cell 2016
38425362 In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis

Gottinger, A, Mascotti, ML, Alvigini, L, Mattevi, A, Nicoll, CR, Cecchini, D, Corana, F, Mannucci, B

Nat Catal 2024
Participants
Participates
Catalyst Activity

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen of COQ3:COQ4:COQ5:COQ6:COQ7:COQ9 [mitochondrial inner membrane]

This event is regulated
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