Acute Endurance Exercise Induces Nuclear p53 Abundance in Human Skeletal Muscle

Purpose: The tumor suppressor protein p53 may have regulatory roles in exercise response-adaptation processes such as mitochondria biogenesis and autophagy, although its cellular location largely governs its biological role. We investigated the subcellular localization of p53 and selected signaling targets in human skeletal muscle following a single bout of endurance exercise. Methods: Sixteen, untrained individuals were pair-matched for aerobic capacity (VO2peak) and allocated to either an exercise (EX, n = 8) or control (CON, n = 8) group. After a resting muscle biopsy, EX performed 60 min continuous cycling at similar to 70% of VO2peak during which time CON subjects rested. A further biopsy was obtained from both groups 3 h post exercise (EX) or 4 h after the first biopsy (CON). Results: Nuclear p53 increased after 3 h recovery with EX only (similar to 48%, p < 0.05) but was unchanged in the mitochondria or cytoplasmic fractions in either group. Autophagy protein 5 (Atg-5) decreased in the mitochondria protein fraction 3 h post-EX (similar to 69%, P < 0.05) but remained unchanged in CON. There was an increase in cytoplasmic levels of the mitophagy marker PINK1 following 3 h of rest in CON only (similar to 23%, P < 0.05). There were no changes in mitochondria, nuclear, or cytoplasmic levels of PGC-1 alpha post-exercise in either group. Conclusions: The selective increase in nuclear p53 abundance following endurance exercise suggests a potential pro-autophagy response to remove damaged proteins and organelles prior to initiating mitochondria biogenesis and remodeling responses in untrained individuals.