Speaker: Halil Aydin, Postdoctoral Scholar - Cellular and Molecular Pharmacology, University of California San Francisco

Title: The Structural Basis of Mitochondrial Coenzyme Q Biosynthesis

Abstract: Coenzyme Q (CoQ) is a redox-active lipid that is essential for cellular respiration, and serves as a cofactor for numerous mitochondrial enzymes and extramitochondrial functions. Most eukaryotic CoQ is produced by the CoQ biosynthetic pathway (~13 known components). A majority of the proteins participate in CoQ production are located on the matrix face of the mitochondrial inner membrane. CoQ biosynthesis is a multi-step process, and the main building blocks of this molecule are successively modified by the mitochondrial inner membrane-associated enzymes (COQ1-11) during CoQ production. These enzymes interact with each other in a highly cooperative manner, and form various subcomplexes and a high molecular weight complex Q in mitochondria. However, the mechanistic  details of this dynamic network of protein-protein interactions and complex Q assembly pathway is not well understood. Here, we report a 2.4 Å electron cryo-microscopy structure of the human COQ7- COQ9 biosynthetic complex. The structure reveals four copies of each molecule forming a hetero-octameric complex. We observe many charge-charge and hydrophobic interactions on three different molecular interfaces between the hydroxylase COQ7 and the lipid-binding COQ9. Our atomic models also show clearly discernible ligand densities inside the hydrophobic cavities of both molecules. Together, we expect to understand the spatial organization of complex Q components, and gain mechanistic insights into the molecular functions that facilitate CoQ biosynthesis.