AMP‐activated protein kinase is required for exercise‐induced peroxisome proliferator‐activated receptor γ co‐activator 1α translocation to subsarcolemmal mitochondria in skeletal muscle
Bibliographic record
Abstract
Key points The transcriptional co‐activator peroxisome proliferator‐activated receptor γ co‐activator 1α (PGC‐1α), in concert with mitochondrial transcription factor A (Tfam), has been implicated in the direct regulation of the mitochondrial genome. In humans, rats and mice, acute exercise was found to promote PGC‐1α translocation to subsarcolemmal (SS) mitochondria. In rats, treatment with 5‐aminoimidazole‐4‐carboxamide‐1‐β‐ribofuranoside induced both PGC‐1α and Tfam translocation and in addition PGC‐1α and Tfam were found to co‐locolize with α‐tubulin. In mice, rendering AMP‐activated protein kinase (AMPK) inactive prevented PGC‐1α translocation. These data suggest that exercise causes translocation of PGC‐1α preferentially to SS mitochondria in an AMPK‐dependent manner. Abstract In skeletal muscle, mitochondria exist as two subcellular populations known as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS mitochondria preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The transcriptional co‐activator peroxisome proliferator‐activated receptor γ co‐activator 1α (PGC‐1α) and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, although SS and IMF differences may exist, and the potential signalling events regulating the mitochondrial content of these proteins have not been elucidated. Therefore, we examined the potential for PGC‐1α and Tfam to translocate to SS and IMF mitochondria in human subjects, and performed experiments in rodents to identify signalling mechanisms regulating these translocation events. Acute exercise in humans and rats increased PGC‐1α content in SS but not IMF mitochondria. Acute exposure to 5‐aminoimidazole‐4‐carboxamide‐1‐β‐ribofuranoside in rats recapitulated the exercise effect of increased PGC‐1α protein within SS mitochondria only, suggesting that AMP‐activated protein kinase (AMPK) signalling is involved. In addition, rendering AMPK inactive (AMPK kinase dead mice) prevented exercise‐induced PGC‐1α translocation to SS mitochondria, further suggesting that AMPK plays an integral role in these translocation events. In contrast to the conserved PGC‐1α translocation to SS mitochondria across species (humans, rats and mice), acute exercise only increased mitochondrial Tfam in rats. Nevertheless, in rat resting muscle PGC‐1α and Tfam co‐immunoprecipate with α‐tubulin, suggesting a common cytosolic localization. These data suggest that exercise causes translocation of PGC‐1α preferentially to SS mitochondria in an AMPK‐dependent manner.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".