Characterizing Coenzyme Q6 Biosynthesis in Saccharomyces cerevisiae and the Role of Coq5 in the Efficient Methylation of Q6-intermediates

Coenzyme Q (ubiquinone or Q) is a lipophilic redox active compound essential for respiration via the electron transport chain. Q is composed of a polyisoprenoid "tail" that anchors to the lipid membrane, and a benzoquinone "head" that confers the abilities to shuttle electrons from Complexes I and II to Complex III. In Saccharomyces cerevisiae, the biosynthesis of Q 6 occurs in the mitochondria inner membrane via eleven nuclear-encoded genes (COQ1-9, ARH1, YAH1), six of which compose a multi-subunit complex termed the CoQ-synthome. The following chapters in this dissertation summarize the body of work completed on various Q6 projects: the partial rescue of yeast coq5 mutants by the human COQ5 homolog only when the CoQ-synthome is assembled (Chapter 2), and the resulting novel Q6-intermediate IDDMQ 6 detected in these coq5 strains via LC/MS-MS (Chapter 3); the localization of Coq-GFP polypeptides in mitochondria but not in peroxisomes via fluorescent microcopy (Chapter 4); and the requirement of de novo folate biosynthesis in yeast from the Q6 head group precursor pABA (Chapter 5).