PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells

Peroxisome proliferator-activated receptor-γ coactivator 1α（PGC-1α） is a transcriptional co-activator involved in mitochondrial biogenesis, respiratory capacity, and oxidative phosphorylation（OXPHOS）. PGC-1α plays an important role in cellular metabolism and is associated with tumorigenesis, suggesting an involvement in cell cycle progression. However, the underlying mechanisms mediating its involvement in these processes remain unclear. To elucidate the signaling pathways involved in PGC-1α function, we established a cell line, CH1 PGC-1α, which stably overexpresses PGC-1α. Using this cell line, we found that over-expression of PGC-1α stimulated extra adenosine triphosphate（ATP） and reduced reactive oxygen species（ROS） production. These effects were accompanied by up-regulation of the cell cycle checkpoint regulators Cyclin D1 and Cyclin B1. We hypothesized that ATP and ROS function as cellular signals to regulate cyclins and control cell cycle progression. Indeed, we found that reduction of ATP levels down-regulated Cyclin D1 but not Cyclin B1, whereas elevation of ROS levels down-regulated Cyclin B1 but not Cyclin D1. Furthermore, both low ATP levels and elevated ROS levels inhibited cell growth, but PGC-1α was maintained at a constant level. Together, these results demonstrate that PGC-1α regulates cell cycle progression through modulation of Cyclin D1 and Cyclin B1 by ATP and ROS. These findings suggest that PGC-1α potentially coordinates energy metabolism together with the cell cycle.