Region-Specific Quantification of 2-Hydroxyglutarate Enantiomers in Murine Brain during Mitochondrial Complex I Deficiency
Bibliographic record
Abstract
The Ndufs4 –/– mouse is a model of mitochondrial Complex I deficiency that contributes to altered production of the tricarboxylic acid cycle metabolites. We hypothesized that l -2-hydroxyglutarate ( l -2-HG) levels would be elevated in the pathologically affected regions of the Ndufs4 –/– mouse brain in parallel with metabolic acidosis. We employed a stable isotope dilution method for the concurrent quantification of l -lactate and the distinct 2-HG enantiomers in isolated mouse brain regions. While lactate levels were elevated, as expected in the Ndufs4 –/– brain, the levels of l -2-HG and the enantiomer d -2-HG were markedly reduced in a region-specific manner, and this decrease was also reproduced in the Ndufs4 –/– serum. The specific and reproducible decreases in 2-HG quantified in Complex I deficiency may have utility as a unique disease biomarker. Quantitative analysis of the mitochondrial proteome of the Ndufs4 –/– mouse brainstem indicated an increased abundance of l -2-HG dehydrogenase, suggesting that 2-HG enantiomers are metabolized in the Ndufs4 –/– mouse yielding FADH 2 to alleviate the bioenergetic deficit.
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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 | 0.001 |
| 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".