The guardian of the genome p53 regulates exercise-induced mitochondrial plasticity beyond organelle biogenesis
Journal article
Smiles, William and Camera, Donny. (2018). The guardian of the genome p53 regulates exercise-induced mitochondrial plasticity beyond organelle biogenesis. Acta Physiologica. 222(3), pp. 1 - 13. https://doi.org/10.1111/apha.13004
Authors | Smiles, William and Camera, Donny |
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Abstract | The Guardian of the Genome p53 has been established as a potent tumour suppressor. However, culminating from seminal findings in rodents more than a decade ago, several studies have demonstrated that p53 is required to maintain basal mitochondrial function [ie, respiration and reactive oxygen species (ROS) homeostasis]. Specifically, via its role(s) as a tumour suppressor, p53 intimately surveys cellular DNA damage, in particular mitochondrial DNA (mtDNA), to ensure that the mitochondrial network is carefully monitored and cell viability is upheld, because aberrant mtDNA damage leads to apoptosis and widespread cellular perturbations. Indeed, data from rodents and humans have demonstrated that p53 forms an integral component of the exercise‐induced signal transduction network regulating skeletal muscle mitochondrial remodelling. In response to exercise‐induced disruptions to cellular homeostasis that have the potential to harm mtDNA (eg, contraction‐stimulated ROS emissions), appropriate p53‐regulated, mitochondrial turnover responses prevail to protect the genome and ultimately facilitate a shift from aerobic glycolysis to oxidative phosphorylation, adaptations critical for endurance‐based exercise that are commensurate with p53's role as a tumour suppressor. Despite these observations, several discrepancies exist between rodent and human studies pinpointing p53 subcellular trafficking from nuclear‐to‐mitochondrial compartments following acute exercise. Such interspecies differences in p53 activity and the plausible p53‐mediated adaptations to chronic exercise training will be discussed herein. |
Keywords | exercise; mitochondria; p53; protein turnover; skeletal muscle |
Year | 2018 |
Journal | Acta Physiologica |
Journal citation | 222 (3), pp. 1 - 13 |
Publisher | Wiley-Blackwell |
ISSN | 1748-1708 |
Digital Object Identifier (DOI) | https://doi.org/10.1111/apha.13004 |
Scopus EID | 2-s2.0-85041131656 |
Page range | 1 - 13 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United Kingdom |
Editors | P. B. Persson |
https://acuresearchbank.acu.edu.au/item/8761q/the-guardian-of-the-genome-p53-regulates-exercise-induced-mitochondrial-plasticity-beyond-organelle-biogenesis
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