Mitochondrial biogenesis elicited by chronic contractile activity with mTORC1 inhibition
Bibliographic record
Abstract
Chronic contractile activity (CCA) enriches the mitochondrial content of skeletal muscle, and this adaptation requires an increased expression of nuclear genes encoding mitochondrial proteins (NUGEMPs). The mammalian target of rapamycin complex 1 (mTORC1) has been implicated in regulating the expression of NUGEMPs by linking the co-activator PGC-1α to the transcription factor YY1. We wished to ascertain if mTORC1 was required for CCA-induced mitochondrial biogenesis. C2C12 myotubes were subjected to CCA (3 hours/day, 4 days) in the presence of 1nM rapamycin, an mTORC1 inhibitor, or DMSO. CCA increased mitochondrial content, as reflected by cytochrome oxidase (COX) activity. This adaptation was also evident in the presence of rapamycin. Indeed, mTORC1 inhibition led to an increase in COX activity in both the absence (28%) and presence (20%) of CCA. Surprisingly, the mTORC1 component raptor, as well as YY1, were both significantly elevated due to mTORC1 inhibition. However, CCA had no effect on raptor levels, but increased YY1 expression by 1.8-fold. State III respiration declined in rapamycin-treated cells, but this was not observed in the presence of CCA, suggesting that CCA recovered mitochondrial function. These data suggest that mTORC1 may be a negative regulator of NUGEMPs, and that the inhibition of mTORC1 does not blunt CCA-induced mitochondrial biogenesis.
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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) | 0.001 | 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 | 0.000 | 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".