Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53–Tfam–mitochondrial DNA complex in skeletal muscle
Bibliographic record
Abstract
Key points p53 is one of several important proteins that regulate the synthesis and function of mitochondria in muscle, and mice lacking p53 have impaired aerobic capacity. The role of p53 in response to physiological stress such as exercise has not been investigated. We demonstrate that acute exercise induces the translocation of p53 to mitochondria, and promotes a subsequent interaction with mitochondrial transcription factor A (Tfam) and mitochondrial DNA (mtDNA) to positively affect mtDNA transcription. This rapid effect on p53 translocation probably represents an early exercise response which can promote long‐term beneficial mitochondrial and metabolic adaptations in muscle. The results could have clinical implications in light of the growing recognition of exercise as an alternative therapy in cancer treatment, and the central role of p53 in halting tumorigenesis. Abstract The major tumour suppressor protein p53 plays an important role in maintaining mitochondrial content and function in skeletal muscle. p53 has been shown to reside in the mitochondria complexed with mitochondrial DNA (mtDNA); however, the physiological repercussions of mitochondrial p53 remain unknown. We endeavoured to elucidate whether an acute bout of endurance exercise could mediate an increase in mitochondrial p53 levels. C57Bl6 mice ( n = 6 per group) were randomly assigned to sedentary, acute exercise (AE, 15 m min −1 for 90 min) or acute exercise + 3 h recovery (AER) groups. Exercise concomitantly increased the mRNA content of nuclear‐encoded (PGC‐1α, Tfam, NRF‐1, COX‐IV, citrate synthase) and mtDNA‐encoded (COX‐I) genes in the AE group, and further by ∼5‐fold in the AER group. Nuclear p53 protein levels were reduced in the AE and AER groups, while in contrast, the abundance of p53 was drastically enhanced by ∼2.4‐fold and ∼3.9‐fold in subsarcolemmal and intermyofibrillar mitochondria, respectively, in the AER conditions. Within the mitochondria, the interaction of p53 with mtDNA at the D‐loop and with Tfam was elevated by ∼4.6‐fold and ∼3.6‐fold, respectively, in the AER group. In the absence of p53, the enhanced COX‐I mRNA content observed with AE and AER was abrogated. This study is the first to indicate that endurance exercise can signal to localize p53 to the mitochondria where it may serve to positively modulate the activity of the mitochondrial transcription factor Tfam. Our findings help us understand the mechanisms underlying the effects of exercise as a therapeutic intervention designed to trigger the pro‐metabolic functions of p53.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".