skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae

Abstract

Coenzyme Q (Q or ubiquinone) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail and is required for mitochondrial electron transport. In the yeast Saccharomyces cerevisiae, Q is synthesized by the products of 11 known genes, COQ1–COQ9, YAH1, and ARH1. The function of some of the Coq proteins remains unknown, and several steps in the Q biosynthetic pathway are not fully characterized. Several of the Coq proteins are associated in a macromolecular complex on the matrix face of the inner mitochondrial membrane, and this complex is required for efficient Q synthesis. In this paper, we further characterize this complex via immunoblotting and proteomic analysis of tandem affinity-purified tagged Coq proteins. We show that Coq8, a putative kinase required for the stability of the Q biosynthetic complex, is associated with a Coq6-containing complex. Additionally Q6 and late stage Q biosynthetic intermediates were also found to co-purify with the complex. A mitochondrial protein of unknown function, encoded by the YLR290C open reading frame, is also identified as a constituent of the complex and is shown to be required for efficient de novo Q biosynthesis. Finally, given its effect on Q synthesis and its association withmore » the biosynthetic complex, we propose that the open reading frame YLR290C be designated COQ11.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Molecular Biology Inst.
  2. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Molecular Biology Inst. UCLA/DOE Inst. for Genomics and Proteomics
  3. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Molecular Biology Inst. UCLA/DOE Inst. for Genomics and Proteomics. Dept. of Biological Chemistry
Publication Date:
Research Org.:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States); National Science Foundation (NSF)
OSTI Identifier:
1348353
Grant/Contract Number:  
FC02-02ER63421; S10RR024605; R01GM103479; MCB-1330803; GM100753
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 290; Journal Issue: 12; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Coenzyme Q; Immunoprecipitation; Mass Spectrometry (MS); Mitochondrial Metabolism; Protein Complex; Proteomics; Q Biosynthetic Intermediates; Saccharomyces cerevisiae; Ubiquinone; Yeast

Citation Formats

Allan, Christopher M., Awad, Agape M., Johnson, Jarrett S., Shirasaki, Dyna I., Wang, Charles, Blaby-Haas, Crysten E., Merchant, Sabeeha S., Loo, Joseph A., and Clarke, Catherine F. Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae. United States: N. p., 2015. Web. doi:10.1074/jbc.m114.633131.
Allan, Christopher M., Awad, Agape M., Johnson, Jarrett S., Shirasaki, Dyna I., Wang, Charles, Blaby-Haas, Crysten E., Merchant, Sabeeha S., Loo, Joseph A., & Clarke, Catherine F. Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae. United States. https://doi.org/10.1074/jbc.m114.633131
Allan, Christopher M., Awad, Agape M., Johnson, Jarrett S., Shirasaki, Dyna I., Wang, Charles, Blaby-Haas, Crysten E., Merchant, Sabeeha S., Loo, Joseph A., and Clarke, Catherine F. 2015. "Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae". United States. https://doi.org/10.1074/jbc.m114.633131. https://www.osti.gov/servlets/purl/1348353.
@article{osti_1348353,
title = {Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae},
author = {Allan, Christopher M. and Awad, Agape M. and Johnson, Jarrett S. and Shirasaki, Dyna I. and Wang, Charles and Blaby-Haas, Crysten E. and Merchant, Sabeeha S. and Loo, Joseph A. and Clarke, Catherine F.},
abstractNote = {Coenzyme Q (Q or ubiquinone) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail and is required for mitochondrial electron transport. In the yeast Saccharomyces cerevisiae, Q is synthesized by the products of 11 known genes, COQ1–COQ9, YAH1, and ARH1. The function of some of the Coq proteins remains unknown, and several steps in the Q biosynthetic pathway are not fully characterized. Several of the Coq proteins are associated in a macromolecular complex on the matrix face of the inner mitochondrial membrane, and this complex is required for efficient Q synthesis. In this paper, we further characterize this complex via immunoblotting and proteomic analysis of tandem affinity-purified tagged Coq proteins. We show that Coq8, a putative kinase required for the stability of the Q biosynthetic complex, is associated with a Coq6-containing complex. Additionally Q6 and late stage Q biosynthetic intermediates were also found to co-purify with the complex. A mitochondrial protein of unknown function, encoded by the YLR290C open reading frame, is also identified as a constituent of the complex and is shown to be required for efficient de novo Q biosynthesis. Finally, given its effect on Q synthesis and its association with the biosynthetic complex, we propose that the open reading frame YLR290C be designated COQ11.},
doi = {10.1074/jbc.m114.633131},
url = {https://www.osti.gov/biblio/1348353}, journal = {Journal of Biological Chemistry},
issn = {0021-9258},
number = 12,
volume = 290,
place = {United States},
year = {2015},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

Figures / Tables:

FIGURE 1 FIGURE 1: Proposed coenzyme Q biosynthetic pathway in S. cerevisiae. Yeast utilize either 4HB or pABA to synthesize the first lipid intermediates of the pathway, HHB or HAB, respectively, through the actions of Coq1 and Coq2. These intermediates then undergo a series of ring modifications catalyzed by the enzymes denotedmore » above each step to yield Q. Two steps in the pathway, denoted with question marks, remain uncharacterized. The step at which the amino group is converted to the hydroxyl group remains unclear and is denoted by dashed arrows. Two late stage intermediates, DMQ6 and IDMQ6, are readily detected in yeast. The hexaprenyl moiety is abbreviated as R.« less

Save / Share:

Works referenced in this record:

A Defect in Coenzyme Q Biosynthesis Is Responsible for the Respiratory Deficiency in Saccharomyces cerevisiae abc1 Mutants
journal, March 2001


A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins
journal, February 2000


Expression of the human atypical kinase ADCK3 rescues coenzyme Q biosynthesis and phosphorylation of Coq polypeptides in yeast coq8 mutants
journal, May 2011


Protein Profiling of Plastoglobules in Chloroplasts and Chromoplasts. A Surprising Site for Differential Accumulation of Metabolic Enzymes
journal, February 2006


para -Aminobenzoic Acid Is a Precursor in Coenzyme Q 6 Biosynthesis in Saccharomyces cerevisiae
journal, June 2010


PPDB, the Plant Proteomics Database at Cornell
journal, October 2008


The Saccharomyces cerevisiae COQ6 Gene Encodes a Mitochondrial Flavin-dependent Monooxygenase Required for Coenzyme Q Biosynthesis
journal, April 2003


Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
journal, August 1970


Tocopherol Cyclase (VTE1) Localization and Vitamin E Accumulation in Chloroplast Plastoglobule Lipoprotein Particles
journal, January 2006


Adrenodoxin Reductase Homolog (Arh1p) of Yeast Mitochondria Required for Iron Homeostasis
journal, October 2000


Endogenous synthesis of coenzyme Q in eukaryotes
journal, June 2007


Sorting Signals, N-Terminal Modifications and Abundance of the Chloroplast Proteome
journal, April 2008


COX15 Codes for a Mitochondrial Protein Essential for the Assembly of Yeast Cytochrome Oxidase
journal, July 1997


Coenzyme Q supplementation or over-expression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants
journal, April 2014


Using Sequence Similarity Networks for Visualization of Relationships Across Diverse Protein Superfamilies
journal, February 2009


CDD: a Conserved Domain Database for the functional annotation of proteins
journal, November 2010


Hydroxylation of demethoxy-Q6 constitutes a control point in yeast coenzyme Q6 biosynthesis
journal, November 2008


Coenzyme Q – Biosynthesis and functions
journal, May 2010


Identification of the Binding Site of the Quinone-Head Group in Mitochondrial Coq10 by Photoaffinity Labeling
journal, June 2014


Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis
journal, October 2014


Network Organization of the Huntingtin Proteomic Interactome in Mammalian Brain
journal, July 2012


Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases
journal, June 2010


Structure of PA4019, a putative aromatic acid decarboxylase from Pseudomonas aeruginosa
journal, September 2011


COQ9 , a New Gene Required for the Biosynthesis of Coenzyme Q in Saccharomyces cerevisiae
journal, July 2005


Yeast Mitochondrial Dehydrogenases Are Associated in a Supramolecular Complex
journal, August 2001


Yeast Coq5 C -Methyltransferase Is Required for Stability of Other Polypeptides Involved in Coenzyme Q Biosynthesis
journal, December 2003


The Genetic Landscape of a Cell
journal, January 2010


Assessing Systems Properties of Yeast Mitochondria through an Interaction Map of the Organelle
journal, January 2006


PET genes of Saccharomyces cerevisiae.
journal, January 1990


CDD: conserved domains and protein three-dimensional structure
journal, November 2012


Crystal structure of a dodecameric FMN-dependent UbiX-like decarboxylase (Pad1) from Escherichia coli O157: H7
journal, November 2004


The Functional Network of the Arabidopsis Plastoglobule Proteome Based on Quantitative Proteomics and Genome-Wide Coexpression Analysis
journal, January 2012


Simultaneous Qualitative and Quantitative Analysis of the Escherichia coli Proteome : A Sweet Tale
journal, January 2006


Chemical and biological evolution of a nucleotide-binding protein
journal, July 1974


Characterization of the COQ5 Gene from Saccharomyces cerevisiae EVIDENCE FOR A C -METHYLTRANSFERASE IN UBIQUINONE BIOSYNTHESIS
journal, April 1997


The role of UbiX in Escherichia coli coenzyme Q biosynthesis
journal, November 2007


The Saccharomyces cerevisiae COQ10 Gene Encodes a START Domain Protein Required for Function of Coenzyme Q in Respiration
journal, October 2005


Ubiquinone biosynthesis in Saccharomyces cerevisiae : the molecular organization of O -methylase Coq3p depends on Abc1p/Coq8p
journal, December 2008


Deciphering key features in protein structures with the new ENDscript server
journal, April 2014


Yeast and Rat Coq3 and Escherichia coli UbiG Polypeptides Catalyze Both O -Methyltransferase Steps in Coenzyme Q Biosynthesis
journal, July 1999


Absolute Quantification of Proteins by LCMS E : A Virtue of Parallel ms Acquisition
journal, October 2005


The Protonmotive Q Cycle in Mitochondria and Bacteria
journal, January 1994


Metabolism and function of coenzyme Q
journal, January 2004


The yeast Coq4 polypeptide organizes a mitochondrial protein complex essential for coenzyme Q biosynthesis
journal, January 2009


Involvement of Mitochondrial Ferredoxin and Para-Aminobenzoic Acid in Yeast Coenzyme Q Biosynthesis
journal, May 2010


The ins and outs of algal metal transport
journal, September 2012


A tRNATRP gene mediates the suppression of cbs2-223 previously attributed to ABC1/COQ8
journal, April 2004


Saccharomyces cerevisiae Coq9 polypeptide is a subunit of the mitochondrial coenzyme Q biosynthetic complex
journal, July 2007


Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q
journal, March 2005


Plastid lipid droplets at the crossroads of prenylquinone metabolism
journal, February 2012


PAD1 and FDC1 are essential for the decarboxylation of phenylacrylic acids in Saccharomyces cerevisiae
journal, June 2010


Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis
journal, November 2014


A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae
journal, April 2013


Regulation of yeast acetohydroxyacid synthase by valine and ATP
journal, August 2001


ABC1K atypical kinases in plants: filling the organellar kinase void
journal, September 2012


Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis
journal, January 2015


MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004


Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations.
journal, June 1990


The molecular genetics of coenzyme Q biosynthesis in health and disease
journal, May 2014


Functional profiling of the Saccharomyces cerevisiae genome
journal, July 2002


Yeast COQ4 Encodes a Mitochondrial Protein Required for Coenzyme Q Synthesis
journal, August 2001


MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0
journal, October 2013


Mitochondrial Ferredoxin Is Required for Heme A Synthesis in Saccharomyces cerevisiae
journal, January 2002


Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane
journal, September 2008


Caloramator viterbensis sp. nov., a novel thermophilic, glycerol-fermenting bacterium isolated from a hot spring in Italy
journal, July 2002


PET genes of Saccharomyces cerevisiae
journal, September 1990


Regulation of yeast acetohydroxyacid synthase by valine and ATP
journal, July 2001


Works referencing / citing this record:

Biosynthesis and applications of prenylquinones
journal, February 2018


The Endoplasmic Reticulum-Mitochondria Encounter Structure Complex Coordinates Coenzyme Q Biosynthesis
journal, January 2019


Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts
journal, January 2019


Reduction in the levels of CoQ biosynthetic proteins is related to an increase in lifespan without evidence of hepatic mitohormesis
journal, September 2018


Biosynthesis of coenzyme Q in eukaryotes
journal, July 2015


Coenzyme Q10 Supplementation in Aging and Disease
journal, February 2018


CoQ10 production in Schizosaccharomyces pombe is increased by reduction of glucose levels or deletion of pka1
journal, April 2019


Investigation of candidate genes involved in the rhodoquinone biosynthetic pathway in Rhodospirillum rubrum
journal, May 2019


Schizosaccharomyces japonicus has low levels of CoQ 10 synthesis, respiration deficiency, and efficient ethanol production
journal, December 2017