One Bout of Aerobic Exercise Elicits Alterations in The Expression of Mitochondrial Unfolded Protein Response (UPRmt) Markers in Skeletal Muscle
Bibliographic record
Abstract
Muscle contractions during aerobic exercise stimulate molecular pathways to promote the production of new mitochondria, and improve their function. These adaptations translate into improved oxygen consumption and metabolic capacity of skeletal muscle. However, the increased drive for mitochondrial biogenesis during contractile activity causes an accumulation of misfolded proteins, disrupting mitochondrial homeostasis. The action of the UPRmt, a cytoprotective stress response pathway, is required to mitigate the associated proteotoxicity. This protein quality control mechanism favours the transcription of mitochondrial chaperones and proteases to refold and degrade the defective proteins, while inhibiting global protein translation. However, the regulation and activity of the UPRmt in helping skeletal muscle adapt to exercise stress during and after an acute bout of exercise has yet to be determined. Thus, to investigate this, mice were separated into sedentary (SED), acute exercise (AE) and acute exercise with recovery (AER) groups (n=4/group). The exercise consisted of 90‐minutes of treadmill running at 15m/min. Tibialis anterior muscles were extracted from the AE groups immediately following exercise and from the AER group 3 hours post‐exercise. Total RNA was isolated and mRNA levels were measured using qPCR. In line with previous data, PGC‐1α mRNA increased by 50% in the AE group and increased further to 3.4‐fold in the AER group. Activating transcription factor 5 (ATF5), an important regulator of UPRmt gene expression, did not change with acute exercise or recovery. ATF4, another transcription factor for stress‐responsive genes, was also unchanged at the end of exercise, but was upregulated by 28% in the recovery period. mRNA levels of downstream targets of ATF5, Lon protease (LonP) and chaperones (HSP60 and GRP75) were upregulated by 18%, 24% and 77%, respectively. HSP60 mRNA returned to control levels during recovery, while GRP75 and LonP mRNAs remained elevated in the AER group. Our data indicate that acute exercise influences the expression of genes involved in both mitochondrial biogenesis and those of the UPRmt, contributing to the maintenance of organelle proteostasis in exercised muscle. Investigating the regulatory mechanisms governing this acute mitochondrial stress response is critical, as preservation of cellular function in the face of exercise‐induced stress is essential for metabolic adaptations in muscle and thus, for whole‐body homeostasis.
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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) | 0.002 | 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".