Multiple signaling pathways regulate contractile activity-mediated PGC-1α gene expression and activity in skeletal muscle cells.

Abstract

PGC‐1α is an important transcriptional coactivator that plays a key role in mediating mitochondrial biogenesis. Within seconds of the onset of contractile activity, a number of rapid cellular events occur that form part of the initial signaling processes involved in PGC‐1α gene regulation, such as elevations in cytoplasmic calcium, AMPK and p38 activation, and elevated ROS production. We observed that basal levels of PGC‐1α promoter activity were more sensitive to resting Ca2+ levels, compared to ROS, p38 or, AMPK signaling. Moreover, enhanced PGC‐1α transcription and post‐translational activity on DNA were a result of the activation of multiple signal transduction pathways during contractile activity of myotubes. AMPK, ROS, and Ca2+ appear to be necessary for the regulation of contractile activity‐induced PGC‐1α gene expression, governed partly through p38 MAPK and CaMKII activity. Whether these signaling pathways are arranged as a linear sequence of events, or as largely independent pathways during contractile activity, remains to be determined.