title: PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells.
abstract: 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 CyclinD1 and CyclinB1. 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 CyclinD1 but not CyclinB1, whereas elevation of ROS levels down-regulated CyclinB1 but not CyclinD1. 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 CyclinD1 and CyclinB1 by ATP and ROS. These findings suggest that PGC-1α potentially coordinates energy metabolism together with the cell cycle.
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.|School of Medicine, Yunnan University, Kunming 650091, China.
authors.forename: Xu-feng
authors.initials: XF
authors.lastname: Fu
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Xiu-yu
authors.initials: XY
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Mei-zhang
authors.initials: MZ
authors.lastname: Li
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China.
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Cui
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D056744:Cyclin B1 / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C534699:CCNB1 protein, human; C530104:CCND1 protein, human; D056744:Cyclin B1; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D019938:Cyclin D1; D000255:Adenosine Triphosphate
keywords: Cell cycle; CyclinB1; CyclinD1; Mitochondria; Oxidative phosphorylation (OXPHOS); Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)
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