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Characterization of Saccharomyces cerevisiae Coenzyme Q Biosynthetic Protein Coq11
Author(s) -
Bradley Michelle C.,
Awad Agape M.,
Allan Christopher M.,
Johnson Jarrett S.,
Shirasaki Dyna I.,
Wang Charles,
BlabyHaas Crysten E.,
Loo Joseph A.,
Clarke Catherine F.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.781.9
Subject(s) - coenzyme q – cytochrome c reductase , biosynthesis , biochemistry , cofactor , protein subunit , saccharomyces cerevisiae , biology , translation (biology) , mitochondrion , mitochondrial matrix , gene , enzyme , cytosol , messenger rna , cytochrome c
Coenzyme Q, also known as ubiquinone or Q, is a redox‐active lipid component of the electron transport chain that functions in cellular energy metabolism. Due to its redox capabilities reduced Q (or QH 2 ) also serves as an important lipid‐soluble antioxidant effective in alleviating lipid peroxidative damage. In Saccharomyces cerevisiae , thirteen known mitochondrial proteins, Coq1‐Coq11, Yah1, and Arh1, drive Q biosynthesis. Many of these Coq polypeptides required for Q production are localized to the matrix side of the mitochondrial inner membrane where they form a high molecular weight, multi‐subunit complex known as the ‘CoQ‐synthome’. Absence of individual Coq proteins causes severe defects in Q biosynthesis, and such coq null mutants lose the ability to respire. However, the functional roles of some Coq polypeptides as well as several steps in the Q biosynthetic pathway remain unknown. Here, we present the identification of a novel mitochondrial protein that associates with the CoQ‐synthome encoded by the open reading frame YLR290C , which we renamed Coq11. Co‐immunoprecipitation and lipid analyses demonstrate that Coq11 interacts with other Coq polypeptides and with Q and Q‐intermediates, and is required for efficient de novo Q biosynthesis. We have begun work towards understanding the functional relationship between Coq11 and its human homolog, NDUFA9. Taken together, this project will provide powerful insights into Q biosynthesis and regulation towards the objective of designing effective therapeutics for diseases caused by Q deficiencies. This research was supported by NSF MCB‐1330803 and the Ruth L. Kirschstein National Research Service Award GM007185. Support or Funding Information NSF MCB‐1330803 and the Ruth L. Kirschstein National Research Service Award GM007185