An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis

Mol Cell. 2019 Feb 21;73(4):763-774.e10. doi: 10.1016/j.molcel.2018.11.033. Epub 2019 Jan 17.


The biosynthesis of coenzyme Q presents a paradigm for how cells surmount hydrophobic barriers in lipid biology. In eukaryotes, CoQ precursors-among nature's most hydrophobic molecules-must somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner membrane. Here, we reveal that this process relies on custom lipid-binding properties of COQ9. We show that COQ9 repurposes the bacterial TetR fold to bind aromatic isoprenes with high specificity, including CoQ intermediates that likely reside entirely within the bilayer. We reveal a process by which COQ9 associates with cardiolipin-rich membranes and warps the membrane surface to access this cargo. Finally, we identify a molecular interface between COQ9 and the hydroxylase COQ7, motivating a model whereby COQ9 presents intermediates directly to CoQ enzymes. Overall, our results provide a mechanism for how a lipid-binding protein might access, select, and deliver specific cargo from a membrane to promote biosynthesis.

Keywords: coenzyme Q; lipid-binding protein; mitochondria; peripheral membrane protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Video-Audio Media

MeSH terms

  • Binding Sites
  • Cardiolipins / metabolism
  • Crystallography
  • Membrane Lipids / metabolism*
  • Mitochondrial Membranes / enzymology*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Transport
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Structure-Activity Relationship
  • Tryptophan
  • Ubiquinone / biosynthesis*
  • Ubiquinone / chemistry
  • Ubiquinone / genetics


  • CAT5 protein, S cerevisiae
  • Cardiolipins
  • Coq9 protein, S cerevisiae
  • Membrane Lipids
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquinone
  • Tryptophan