Alterations in mitochondrial function in fibroblasts from patients with Leigh Syndrome French Canadian type (LSFC)
Bibliographic record
Abstract
LSFC is a monogenic metabolic disease characterized by 1) cytochrome c oxidase deficiency, resulting from a mutation in the leucine‐rich pentatricopeptide repeat motif containing gene LRPPRC, and 2) episodes of lactic acidosis “crisis” leading to death early in life. The mechanisms responsible for these crises remain to be elucidated. In this study, we used fibroblasts from LSFC patients as a working model to test the hypothesis that impaired mitochondrial function and network dynamics in these cells may predispose them to premature death. Calcium retention capacity (CRC), oxygen (O 2 ) consumption, reactive oxygen species production, mitochondrial membrane potential (ΔΨ) and network morphology were assessed in intact or permeabilized control and LSFC fibroblasts. Compared to controls, LSFC fibroblasts showed multiple abnormalities under basal condition, including decreased CRC (36%), O 2 consumption (30–59%), ΔΨ (67%) and increased mitochondrial fission. In addition, nutrient overload, which induces premature death of LSFC fibroblasts (FASEB J 2011 25:722.15), exacerbated mitochondrial fission in these cells. Together, these results suggest that mitochondria from LSFC fibroblasts are dysfunctional and this may limit the capacity of these cells to maintain homeostasis, particularly under conditions of nutrient overload. (Supported by: Association de l'acidose lactique and CIHR Emerging Team Grants)
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".