Acute endurance exercise increases the nuclear abundance of PGC-1α in trained human skeletal muscle

Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ. Acute endurance exercise increases the nuclear abundance of PGC-1 alpha in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 298: R912-R917, 2010. First published January 27, 2010; doi: 10.1152/ajpregu.00409.2009.-Peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha) is a transcriptional coactivator that plays a key role in coordinating mitochondrial biogenesis. Recent evidence has linked p38 MAPK and AMPK with activation of PGC-1 alpha. It was recently shown in rodent skeletal muscle that acute endurance exercise causes a shift in the subcellular localization of PGC-1 alpha from the cytosol to the nucleus, allowing PGC-1 alpha to coactivate transcription factors and increase mitochondrial gene expression, but human data are limited and equivocal in this regard. Our purpose was to examine p38 MAPK and AMPK activation, and PGC-1 alpha protein content in whole muscle, cytosolic, and nuclear fractions of human skeletal muscle following an acute bout of endurance exercise. Eight trained men (29 +/- 3 yr; (V) over dotO(2peak) = 55 +/- 2 ml.kg(-1).min(-1)) cycled for 90 min at similar to 65% of (V) over dotO(2peak) and needle biopsy samples (vastus lateralis) were obtained before and immediately after exercise. At rest, the majority of PGC-1 alpha was detected in cytosolic compared with the nuclear fractions. In response to exercise, nuclear PGC-1 alpha protein increased by 54% (P < 0.05), yet whole muscle PGC-1 alpha protein was unchanged compared with rest. Whole muscle and cytosolic p38 MAPK phosphorylation increased several-fold immediately after exercise compared with rest (P < 0.05). Acetyl CoA carboxylase (ACC) phosphorylation, a marker of AMPK activation, was increased by similar to 5-fold in cytosolic fractions following exercise (P < 0.05). These data provide evidence that, in human skeletal muscle, activation of cytosolic p38 MAPK and AMPK may be potential signals that lead to increased nuclear abundance and activation of PGC-1 alpha in response to an acute bout of endurance exercise.