Reactome | COQ6 hydroxylates DHB

COQ6 hydroxylates DHB

Stable Identifier

R-HSA-2162187

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial inner membrane, mitochondrial matrix

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, Mühlenhoff, U, Webert, H, Lill, R, Fontecave, M, Pierrel, F	Chem Biol	2011
31379988	Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells Lacking COQ6 Acosta Lopez, MJ, Trevisson, E, Canton, M, Vázquez-Fonseca, L, Morbidoni, V, Baschiera, E, Frasson, C, Pelosi, L, Rascalou, B, Desbats, MA, Alcázar-Fabra, M, Ríos, JJ, Sánchez-García, A, Basso, G, Navas, P, Pierrel, F, Brea-Calvo, G, Salviati, L	Oxid Med Cell Longev	2019
21540551	COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness Heeringa, SF, Chernin, G, Chaki, M, Zhou, W, Sloan, AJ, Ji, Z, Xie, LX, Salviati, L, Hurd, TW, Vega-Warner, V, Killen, PD, Raphael, Y, Ashraf, S, Ovunc, B, Schoeb, DS, McLaughlin, HM, Airik, R, Vlangos, CN, Gbadegesin, R, Hinkes, B, Saisawat, P, Trevisson, E, Doimo, M, Casarin, A, Pertegato, V, Giorgi, G, Prokisch, H, Rötig, A, Nürnberg, G, Becker, C, Wang, S, Ozaltin, F, Topaloglu, R, Bakkaloglu, A, Bakkaloglu, SA, Müller, D, Beissert, A, Mir, S, Berdeli, A, Varpizen, S, Zenker, M, Matejas, V, Santos-Ocaña, C, Navas, P, Kusakabe, T, Kispert, A, Akman, S, Soliman, NA, Krick, S, Mundel, P, Reiser, J, Nürnberg, P, Clarke, CF, Wiggins, RC, Faul, C, Hildebrandt, F	J Clin Invest	2011
37476682	Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature Hojabri, M, Gilani, A, Irilouzadian, R, Nejad Biglari, H, Sarmadian, R	Clin Med Insights Case Rep	2023
24270420	ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption Ashraf, S, Gee, HY, Woerner, S, Xie, LX, Vega-Warner, V, Lovric, S, Fang, H, Song, X, Cattran, DC, Avila-Casado, C, Paterson, AD, Nitschké, P, Bole-Feysot, C, Cochat, P, Esteve-Rudd, J, Haberberger, B, Allen, SJ, Zhou, W, Airik, R, Otto, EA, Barua, M, Al-Hamed, MH, Kari, JA, Evans, J, Bierzynska, A, Saleem, MA, Bockenhauer, D, Kleta, R, El Desoky, S, Hacihamdioglu, DO, Gok, F, Washburn, J, Wiggins, RC, Choi, M, Lifton, RP, Levy, S, Han, Z, Salviati, L, Prokisch, H, Williams, DS, Pollak, M, Clarke, CF, Pei, Y, Antignac, C, Hildebrandt, F	J Clin Invest	2013
36843884	Clinical features and gene variation analysis of COQ8B nephropathy: Report of seven cases Liang, R, Chen, X, Zhang, Y, Law, CF, Yu, S, Jiao, J, Yang, Q, Wu, D, Zhang, G, Chen, H, Wang, M, Yang, H, Wang, A	Front Pediatr	2022
38141230	Activation of Coq6p, a FAD Monooxygenase Involved in Coenzyme Q Biosynthesis, by Adrenodoxin Reductase/Ferredoxin Gonzalez, L, Chau-Duy Tam Vo, S, Faivre, B, Pierrel, F, Fontecave, M, Hamdane, D, Lombard, M	Chembiochem	2024
12721307	The Saccharomyces cerevisiae COQ6 gene encodes a mitochondrial flavin-dependent monooxygenase required for coenzyme Q biosynthesis Gin, P, Hsu, AY, Rothman, SC, Jonassen, T, Lee, PT, Tzagoloff, A, Clarke, CF	J Biol Chem	2003
27499296	Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function Floyd, BJ, Wilkerson, EM, Veling, MT, Minogue, CE, Xia, C, Beebe, ET, Wrobel, RL, Cho, H, Kremer, LS, Alston, CL, Gromek, KA, Dolan, BK, Ulbrich, A, Stefely, JA, Bohl, SL, Werner, KM, Jochem, A, Westphall, MS, Rensvold, JW, Taylor, RW, Prokisch, H, Kim, JP, Coon, JJ, Pagliarini, DJ	Mol Cell	2016
38425362	In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis Nicoll, CR, Alvigini, L, Gottinger, A, Cecchini, D, Mannucci, B, Corana, F, Mascotti, ML, Mattevi, A	Nat Catal	2024

Participants

Input

Output

Participates

as an event of

Ubiquinol biosynthesis (Homo sapiens)

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]

Physical Entity

COQ3:COQ4:COQ5:COQ6:COQ7:COQ9 [mitochondrial inner membrane] (Homo sapiens)

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 (GO:0016709)

This event is regulated

Requirements