Coenzyme Q (ubiquinone or CoQ) is an essential lipid that plays a role in mitochondrial respiratory electron transport and serves as an important antioxidant. In human and yeast cells, CoQ synthesis derives from aromatic ring precursors and the isoprene biosynthetic pathway. Saccharomyces cerevisiae coq mutants provide a powerful model for our understanding of CoQ biosynthesis. This review focusses on the biosynthesis of CoQ in yeast and the relevance of this model to CoQ biosynthesis in human cells. The COQ1–COQ11 yeast genes are required for efficient biosynthesis of yeast CoQ. Expression of human homologs of yeast COQ1–COQ10 genes restore CoQ biosynthesis in the corresponding yeast coq mutants, indicating profound functional conservation. Thus, yeast provides a simple yet effective model to investigate and define the function and possible pathology of human COQ (yeast or human gene involved in CoQ biosynthesis) gene polymorphisms and mutations. Biosynthesis of CoQ in yeast and human cells depends on high molecular mass multisubunit complexes consisting of several of the COQ gene products, as well as CoQ itself and CoQ intermediates. The CoQ synthome in yeast or Complex Q in human cells, is essential for de novo biosynthesis of CoQ. Although some human CoQ deficiencies respond to dietary supplementation with CoQ, in general the uptake and assimilation of this very hydrophobic lipid is inefficient. Simple natural products may serve as alternate ring precursors in CoQ biosynthesis in both yeast and human cells, and these compounds may act to enhance biosynthesis of CoQ or may bypass certain deficient steps in the CoQ biosynthetic pathway.

A multitarget real-time PCR (MRT-PCR) for detection of

Loss of the endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) complex that resides in contact sites between the yeast ER and mitochondria leads to impaired respiration; however, the reason for that is not clear. We find that in ERMES null mutants, there is an increase in the level of mRNAs encoding for biosynthetic enzymes of coenzyme Q6 (CoQ6), an essential electron carrier of the mitochondrial respiratory chain. We show that the mega complexes involved in CoQ6 biosynthesis (CoQ synthomes) are destabilized in ERMES mutants. This, in turn, affects the level and distribution of CoQ6 within the cell, resulting in reduced mitochondrial CoQ6. We suggest that these outcomes contribute to the reduced respiration observed in ERMES mutants. Fluorescence microscopy experiments demonstrate close proximity between the CoQ synthome and ERMES, suggesting a spatial coordination. The involvement of the ER-mitochondria contact site in regulation of CoQ6 biogenesis highlights an additional level of communication between these two organelles.

Coenzyme Q (ubiquinone or Q) functions as an essential redox‐active lipid in respiratory electron and proton transport in cellular energy metabolism, and it is an important lipid‐soluble antioxidant in cellular membranes. In Saccharomyces cerevisiae, proteins Coq3‐Coq9, as well as Coq11, assemble into a multi‐subunit protein complex called the CoQ‐synthome, which is required for Q biosynthesis. Coq10, a putative steroidogenic acute regulatory (StAR)‐related lipid transfer (StART) domain protein is not a member of the CoQ‐synthome, but is required for the proper assembly of the CoQ‐synthome, efficient de novo Q biosynthesis during early‐log phase, and the function of Q in respiration and as an antioxidant. Humans possess two isoforms, namely COQ10A and COQ10B. Based on the RNA‐seq data from NCBI, COQ10A is predominantly expressed in heart while COQ10B is present in all tissues, suggesting that COQ10B is probably serving a more general role. Previous studies have shown rescue of S. cerevisiae coq10Δ respiration deficient phenotype by expression of human COQ10A. Here we present new evidence showing rescue of S. cerevisiae coq10Δ by expression of either the human COQ10A or COQ10B homolog, as determined by restoration of respiratory growth on non‐fermentable carbon sources, de novo Q biosynthesis, as well as restoration of the CoQ‐synthome. Support or Funding Information This research was supported by NSF MCB‐1330803 and Ruth L. Kirschstein National Research Service Award GM007185. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Terpenoid quinones are liposoluble redox-active compounds that serve as essential electron carriers and anti-oxidants. One such quinone, rhodoquinone (RQ), couples the respiratory electron transfer chain to the reduction of fumarate to facilitate anaerobic respiration. This mechanism allows RQ-synthesizing organisms to operate their respiratory chain using fumarate as a final electron acceptor. RQ biosynthesis is restricted to a handful of prokaryotic and eukaryotic organisms, and details of this biosynthetic pathway remain enigmatic. One gene, rquA, was discovered to be required for RQ biosynthesis in Rhodospirillum rubrum. However, the function of the gene product, RquA, has remained unclear. Here, using reverse genetics approaches, we demonstrate that RquA converts ubiquinone to RQ directly. We also demonstrate the first in vivo synthetic production of RQ in Escherichia coli and Saccharomyces cerevisiae, two organisms that do not natively produce RQ. These findings help clarify the complete RQ biosynthetic pathway in species which contain RquA homologs.