Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin
Bibliographic record
Abstract
Mitochondrial dysfunction is implicated in the pathogenesis of the neurological condition Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay (ARSACS), yet precisely how mitochondrial metabolism is affected is unknown. Thus, to better understand changes in mitochondrial metabolism caused by loss of the sacsin protein (encoded by the SACS gene, that is mutated in ARSACS) we performed mass spectrometry-based tracer analysis, with both glucose and glutamine traced carbon. Comparing the metabolite profiles between wild-type and sacsin-knockout cell lines revealed increased reliance on aerobic glycolysis in sacsin-deficient cells, as evidenced by the increase in lactate and reduction of glucose. Moreover, sacsin knockout cells differentiated towards a neuronal phenotype had increased levels of tricarboxylic acid cycle metabolites relative to controls. We also observed disruption in the glutaminolysis pathway in differentiated and undifferentiated cells in the absence of sacsin. In conclusion, this work demonstrates consequences for cellular metabolism associated with loss of sacsin, which may be relevant to ARSACS.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".