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Comment
. 2019 Apr 18;26(4):465-467.
doi: 10.1016/j.chembiol.2019.04.005.

Ubiquinone Biosynthetic Complexes in Prokaryotes and Eukaryotes

Affiliations
Comment

Ubiquinone Biosynthetic Complexes in Prokaryotes and Eukaryotes

Hui S Tsui et al. Cell Chem Biol. .

Abstract

Ubiquinone (UQ) is a conserved polyprenylated lipid essential to cellular respiration. Two papers, one in this issue of Cell Chemical Biology (Hajj Chehade et al., 2019) and another in Molecular Cell (Lohman et al., 2019), identify lipid-binding proteins that play crucial roles in chaperoning UQ-intermediates.

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Conflict of interest statement

Declaration of Interests

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.
A 1 MDa soluble metabolon synthesizes UQ8 in E. coli. The long octaprenyl tail of UQ8 and UQ8-intermediates in E. coli are thought to reside at the midplane of the membrane bilayer. Chehade et al. (2019) show that octaprenyl phenol (OPP), an early intermediate in E. coli UQ8 biosynthesis, is converted in six steps to the final product UQ8H2, by a high molecular mass soluble metabolon located in the cytosol. Five Ubi enzymes (shown in blue and pink) are organized around the accessory proteins UbiJ and UbiK. UbiJ contains a sterol carrier protein 2 (SCP2) domain, responsible for binding the UQ8-intermediates. The steps whereby OPP is extracted from the membrane and the UQ8H2 product is delivered back to the membrane are designated by the dashed arrows and represent intriguing and unknown trafficking steps (??).
Figure 2.
Figure 2.
The steps of UQ8 biosynthesis in E. coli. IspB produces octaprenyl-diphosphate. The octaprenyl group (designated by R) is transferred to 4-hydroxybenzoic acid (4HB) by UbiA, to form 3-octaprenyl-4-hydroxybenzoic acid (OHB). UbiD and UbiX work together to mediate decarboxylation and produce octaprenyl phenol (OPP). OPP is then subjected to alternating steps of hydroxylation (shown in blue) and methylation (shown in pink) in the order of UbiI, UbiG, UbiH, UbiE, UbiF and UbiG to form the fully substituted product, UQ8H2. UbiJ and UbiK are required accessory proteins, and UbiJ binds OPP and the other UQ8-intermediates. The order of steps in eukaryotic UQ biosynthesis is slightly different. The first hydroxylation and methylation steps in yeast and human cells are thought to precede the decarboxylation step.

Comment on

  • An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis.
    Lohman DC, Aydin D, Von Bank HC, Smith RW, Linke V, Weisenhorn E, McDevitt MT, Hutchins P, Wilkerson EM, Wancewicz B, Russell J, Stefely MS, Beebe ET, Jochem A, Coon JJ, Bingman CA, Dal Peraro M, Pagliarini DJ. Lohman DC, et al. Mol Cell. 2019 Feb 21;73(4):763-774.e10. doi: 10.1016/j.molcel.2018.11.033. Epub 2019 Jan 17. Mol Cell. 2019. PMID: 30661980 Free PMC article.
  • A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone.
    Hajj Chehade M, Pelosi L, Fyfe CD, Loiseau L, Rascalou B, Brugière S, Kazemzadeh K, Vo CD, Ciccone L, Aussel L, Couté Y, Fontecave M, Barras F, Lombard M, Pierrel F. Hajj Chehade M, et al. Cell Chem Biol. 2019 Apr 18;26(4):482-492.e7. doi: 10.1016/j.chembiol.2018.12.001. Epub 2019 Jan 24. Cell Chem Biol. 2019. PMID: 30686758

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