Premium
Nutrient sensing and mitochondrial coenzyme Q biosynthesis: Are they connected by a phosphatase?
Author(s) -
Awad Agape M.,
Venkataramanan Srivats,
Nag Anish,
Bradley Michelle C.,
Galivanche Anoop R.,
Johnson Tracy L.,
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.782.15
Subject(s) - coenzyme q – cytochrome c reductase , biochemistry , biosynthesis , biology , mitochondrion , ferredoxin , saccharomyces cerevisiae , respiratory chain , mitochondrial respiratory chain , oxidative phosphorylation , yeast , gene , cytochrome c , enzyme
Coenzyme Q (also termed ubiquinone or Q) is an electron carrier in the mitochondrial respiratory chain that functions as an essential component in energy metabolism processes. Q transfers electrons from NADH and succinate to cytochrome c , a heme protein, and also serves as a vital lipid soluble antioxidant. Sufficient de novo Q biosynthesis is crucial for human health. Saccharomyces cerevisiae (baker's yeast) serves as an excellent model for studies on Q because of its powerful molecular genetics and the functional identity of yeast and human COQ genes in Q biosynthesis and function. Coenzyme Q biosynthesis in S. cerevisiae (which makes Q 6 with six isoprene units, versus Q 10 in humans with ten isoprene units) takes place in the mitochondria and, currently, thirteen known mitochondrial proteins are responsible for facilitating this process—Coq1‐Coq11, Yah1 (ferredoxin), and Arh1 (ferredoxin reductase). Many of the proteins necessary for the biosynthesis of Q 6 associate in a high molecular weight complex (termed the “CoQ‐Synthome”) that localizes in the inner mitochondrial membrane. Previous work indicated that the stability of the Q biosynthetic complex relied on the presence of Coq8, the putative kinase of the system. In addition, several Coq polypeptides are phosphorylated in a Coq8‐dependent manner, including Coq3, Coq5, and Coq7, and potentially Coq6. Thus, the role of phosphorylation, as it pertains to Q biosynthesis and regulation, may provide novel information as to how the CoQ‐synthome is regulated. Additionally, intriguing links have been discovered that relate Coq polypeptides and phosphorylation status with nutrient availability and regulatory genes. Hence, our objectives are to investigate these links further and discover new information related to regulation by phosphorylation of the CoQ‐Synthome. Such studies will aid our understanding and treatment of multiple diseases caused by CoQ‐deficiencies and will provide novel insight in longevity and issues related to aging in humans. This research was supported by NSF MCB‐1330803. Support or Funding Information NSF MCB‐1330803