? Coenzyme Q (CoQ), in addition to its role as an electron carrier in the mitochondria! respiratory chain, plays other important functions, including the regulation of permeability transition pores and the prevention of oxidative damage. Thus, abnormal CoQ function could lead to several physiological defects. Coq6, a mitochondria! inner membrane protein, is required for CoQ biosynthesis. Although its exact function is not known, Coq6 shares a high degree of sequence similarity to flavin-dependent monooxygenases, and has a high sequence identity to UbiH, an ? coli hydroxylase involved in CoQ biosynthesis. Consequently, Coq6 is believed to catalyze the analogous step in yeast CoQ biosynthesis. My research proposal will investigate the role of Coq6 using genetic, biochemical and analytical techniques.
The specific aims of this proposal include the identification of the substrate(s) of Coq6 by lipid analysis of select cog6 mutants which accumulate a diagnostic intermediate, and the identification of possible partner proteins and cofactors associated with oq6. This proposal will also evaulate the catalytic similarity between Coq6 and its E. coli homolog, UbiH. The amino acid residues necessary for the stability of the Coq6 polypeptide will also be examined. ? ? ?
