Elevated cellular accumulation of endogenous and exogenous CoQ by altered intracellular trafficking
Bibliographic record
Abstract
Coenzyme Q (CoQ) is produced in the inner membrane of mitochondria, from where it is transported to other cellular membranes. Cellular CoQ levels drop when its synthesis is interrupted, indicating that it can be degraded or eliminated in some way by currently still uncharacterized mechanisms. Low cellular iron availability has been found to lower CoQ levels, at least in part by inhibiting the action of the CoQ biosynthetic enzyme COQ7. These findings prompted us to test the effect of elevated intracellular iron content on CoQ levels. In the mouse macrophage cell line RAW264.7, we found that supplementation with ferrous ions (Fe 2+ ) boosts CoQ levels rapidly and reversibly. Iron loading also increases the cellular accumulation of exogenous CoQ 10 provided in the media. N-acetyl cysteine significantly attenuates the elevation of CoQ levels by iron, suggesting that the effect of iron is mediated by a redox mechanism, although overall cellular reactive oxygen species (ROS) levels were not affected. Treating RAW264.7 cells with the ROS-generator paraquat also dramatically increases CoQ, further pointing to a redox mechanism. No effect on the abundance of several COQ proteins was observed after iron or paraquat treatment, indicating that their effect on CoQ levels is unlikely to arise from altered mitochondrial CoQ synthesis. In contrast, we observed that targeting lysosome function also affects CoQ levels, suggesting that the effects we observe relate to degradation and/or recycling. Our study suggests that targeting these mechanisms could allow for new therapeutic options to boost cellular CoQ levels in patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".