Nutrient sensing and mitochondrial Coenzyme Q biosynthesis: Are they connected by a phosphatase?

Abstract

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, while also serving 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. Coenzyme Q biosynthesis in S. cerevisiae occurs in the mitochondria and, currently, fourteen known mitochondrial proteins are responsible for facilitating this process—Coq1–Coq11, Yah1 (ferredoxin), Arh1 (ferredoxin reductase), and Hfd1 (aldehyde dehydrogenase). Many of the Coq proteins associate in a high molecular weight complex (“CoQ‐Synthome”) that localizes in the inner mitochondrial membrane. Previous work indicated that the stability of the Q biosynthetic complex (as well as the phosphorylation status of several Coq polypeptides, including Coq3, Coq5, Coq7, and potentially Coq6) relied on the presence of Coq8, the putative kinase of the system. Thus, the role of phosphorylation may provide novel information as to how the CoQ‐synthome is regulated. Indeed, intriguing links have been discovered that relate Coq polypeptides and phosphorylation status with nutrient availability and regulatory genes. Most recently, a link has been found between a nutrient sensing gene, SNF2, and the spicing efficiency of PTC7, the phosphatase responsible for controlling a key regulation site in Q biosynthesis. Our objectives are to further investigate these regulatory links. Such studies will aid our understanding and treatment of multiple diseases caused by CoQ‐deficiencies and provide novel insight in longevity and issues related to aging in humans.Support or Funding InformationThis work was supported by the National Science Foundation, Grant MCB‐1330803 and the National Institute of General Medical Sciences (GM‐085474), Whitcome Pre‐doctoral Fellowship in Molecular Biology, and the Ruth L. Kirschstein National Service Award GM‐007185.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.