Saccharomyces cerevisiae Coq10, A Putative START Domain Protein Binds Coenzyme Q And Late‐Stage Q‐Biosynthetic Intermediates

Abstract

Coenzyme Q (ubiquinone or Q) functions as an essential redox‐active lipid in respiratory electron and proton transport in cellular energy metabolism, and is an important lipid‐soluble antioxidant in cellular membranes. In Saccharomyces cerevisiae, at least 13 nuclear‐encoded genes COQ1‐COQ11, YAH1, and ARH1 have been identified as necessary for Q biosynthesis and its function in respiration and as an antioxidant. Many of the Coq polypeptides responsible for Q biosynthesis assemble into a high molecular weight, multi‐subunit complex localized to the matrix side of the mitochondrial inner membrane. This study focuses on characterizing the Coq10 polypeptide, a putative steroidogenic acute regulatory (StAR)‐related lipid transfer (StART) domain protein in S. cerevisiae. Unlike Q‐less coq1‐coq9 deletion mutants, yeast coq10 null mutants contain near wild‐type steady‐state levels of Q6, but are nonetheless respiratory deficient. Yeast coq10 null mutants show decreased de novo Q biosynthesis and accumulate high levels of the early Q‐intermediates, especially during early log phase of growth. The structure of Caulobacter crescentus CC1736, an ortholog of yeast Coq10, contains a hydrophobic tunnel characteristic of StART domain proteins. Purified CC1736 is capable of binding Q and a farnesylated analog of a late‐stage Q biosynthetic intermediate. Overexpression of CC1736 in the coq10 null mutant is able to rescue the respiratory‐deficient phenotype and partially restore efficient Q biosynthesis, suggesting a strong functional conservation. These observations suggest the Coq10 StART domain protein is required for efficient Q biosynthesis, crucial for Q function in respiratory electron transport, and for Q to function as an antioxidant. Coq10 is speculated to be a Q‐binding protein interacting with the multi‐subunit Coq polypeptide complex and/or respiratory complexes, facilitating final delivery of Q from its site of synthesis to sites of function. In order to better understand the biological function of yeast Coq10 we describe the isolation and characterization of the high molecular weight Coq10 oligomer and are characterizing lipid ligand interactions with mature Coq10. The results will provide important clues about the physiological role of Coq10 as well as the molecular interactions required for its function. This research was supported by NSF MCB‐1330803 and Ruth L. Kirschstein National Research Service Award GM007185.Support or Funding InformationThis research was supported by NSF MCB‐1330803 and Ruth L. Kirschstein National Research Service Award GM007185.