The role of Parkin in the maintenance of normal mitochondrial and cellular function in skeletal muscle
Bibliographic record
Abstract
The E3 ligase Parkin has been implicated in the regulation of mitophagy, a quality control process whereby defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson but its role in other tissues remains unknown. In this study, we used a murine model of Parkin deficiency to test the hypothesis that Parkin is important for mitochondrial quality control in the mitochondria‐rich skeletal muscle, a tissue in which autophagy/mitophagy play an important regulatory role. Our results indicate that Parkin is abundant in normal skeletal muscle, and that Parkin deficiency leads to mitochondria‐related abnormalities including 1) lower respiratory rates and acceptor control ratio, 2) reduced activities of respiratory chain complexes containing mtDNA encoded subunits, 3) increased susceptibility to opening of the permeability transition pore, and 4) increased expression of Bnip3 and Bax, which respectively regulate mitophagy and apoptosis. Parkin deficiency is also associated with an increased expression of ER‐stress markers (CHOP, GRP78), and a greater proportion of enlarged muscle fibers, which suggest broader phenotypic changes within skeletal muscle. Overall, these results establish the role of Parkin in the maintenance of normal mitochondrial function in skeletal muscle.
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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 | 0.000 | 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 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".