Autophagy and mitophagy flux in skeletal muscle during chronic‐contractile activity
Bibliographic record
Abstract
Autophagy and mitophagy are important cellular recycling mechanisms, however the regulation of autophagy and mitophagy flux in training‐induced muscle adaptations remains to be elucidated. Using the microtubule destabilizer colchicine (0.04 mg/kg), this study assessed LC3II and p62 flux in skeletal muscles of Sprague‐Dawley rats (501 ± 9 g) subjected to chronic contractile activity (CCA; 3 hours/day, 9V, 10 Hz continuous, 0.1 ms pulse duration) for 1, 2, 3, 5, and 7 days (N=6–8/group). Colchicine was given via an intraperitoneal injection 48 hours prior to tissue collection, whereas control animals were administered saline as a vehicle treatment. Following 7 days of CCA, there were significant increases in maximal state 3 respiration, accompanied by a decrease in ROS production in IMF mitochondria ( P < 0.05), indicating that mitochondrial adaptations were elicited in the stimulated muscle. Notably, whole muscle autophagy flux, as measured by LC3II and p62, was downregulated in response to 3 days of CCA, and further by 7 days of CCA ( P < 0.05). In addition, muscle mitochondrial LC3II flux was decreased by 3 days of CCA, indicative of reduced mitophagy. In contrast, the lysosomal system, measured by TFEB and LAMP1 protein levels, was gradually upregulated by CCA, culminating at day 7. Interestingly, the translocation of TFEB into the nucleus in response to CCA was increased at day 3 ( P < 0.05). However, this nuclear TFEB was not sustained and subsequently declined back to basal levels. In conclusion, we suggest that chronic exercise can lead to muscle adaptations through a coordinated mechanism, involving a decrease in autophagy/mitophagy flux, combined with an increase in the capacity of the lysosomal system. Support or Funding Information This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 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".