Characterization of CoQ‐Synthome proteins and binding partners, their phosphorylation status, and regulation
Bibliographic record
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. 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 its close homology to human 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 are associated together 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. Recent investigation has uncovered a physical association of Coq8 with Coq6, a flavin‐dependent monooxygenase and member of the CoQ‐synthome. Currently, we are investigating the role of phosphorylation, as it pertains to Q biosynthesis and regulation. Mainly, our research aims to: 1) investigate phosphorylation of Coq6 and associated Coq proteins, 2) conduct site‐directed mutagenesis of potential Coq6 phosphorylated residues and assess their effects on the content of Q/Q‐intermediates and yeast growth phenotypes, and 3) characterize the nature of the Coq6‐Coq8 specific interaction. Overall, Coq6 may be an ideal site for regulation since the monooxygenase activity of this protein occurs very early in the pathway, and generates potentially toxic catechol‐containing Q‐intermediates. Our objectives are to investigate this further and discover new information related to regulation by phosphorylation of the CoQ‐Synthome. Support or Funding Information This research was funded by NSF MCB 1330803.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".