Structure and functionality of a multimeric human COQ7:COQ9 complex

Mol Cell. 2022 Nov 17;82(22):4307-4323.e10. doi: 10.1016/j.molcel.2022.10.003. Epub 2022 Oct 27.


Coenzyme Q (CoQ) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined "complex Q" metabolon. Here, we present structure-function analyses of a lipid-, substrate-, and NADH-bound complex comprising two complex Q subunits: the hydroxylase COQ7 and the lipid-binding protein COQ9. We reveal that COQ7 adopts a ferritin-like fold with a hydrophobic channel whose substrate-binding capacity is enhanced by COQ9. Using molecular dynamics, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for the CoQ intermediates to translocate from the bilayer to the proteins' lipid-binding sites. Two such tetramers assemble into a soluble octamer with a pseudo-bilayer of lipids captured within. Together, these observations indicate that COQ7 and COQ9 cooperate to access hydrophobic precursors within the membrane and coordinate subsequent synthesis steps toward producing CoQ.

Keywords: COQ7; COQ9; coenzyme Q; di-iron proteins; mitochondria; protein-lipid complex; protein-membrane interaction; quinone biosynthesis.

Publication types

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

MeSH terms

  • Carrier Proteins
  • Humans
  • Lipids
  • Mitochondrial Membranes* / metabolism
  • Ubiquinone* / chemistry


  • ubiquinone 9
  • ubiquinone 7
  • Ubiquinone
  • Carrier Proteins
  • Lipids