Full Text:   <1343>

Summary:  <370>

Suppl. Mater.: 

CLC number: Q25

On-line Access: 2016-02-01

Received: 2015-06-26

Revision Accepted: 2015-09-14

Crosschecked: 2016-01-13

Cited: 5

Clicked: 1834

Citations:  Bibtex RefMan EndNote GB/T7714


Xu-feng Fu


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.2 P.136-146


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

Author(s):  Xu-feng Fu, Kun Yao, Xing Du, Yan Li, Xiu-yu Yang, Min Yu, Mei-zhang Li, Qing-hua Cui

Affiliation(s):  School of Life Sciences, Yunnan University, Kunming 650091, China; more

Corresponding email(s):   cuiqinghua@ynu.edu.cn

Key Words:  Peroxisome proliferator-activated receptor-γ, coactivator 1α, (PGC-1α, ), Mitochondria, Oxidative phosphorylation (OXPHOS), Cell cycle, CyclinD1, CyclinB1

Xu-feng Fu, Kun Yao, Xing Du, Yan Li, Xiu-yu Yang, Min Yu, Mei-zhang Li, Qing-hua Cui. PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells[J]. Journal of Zhejiang University Science B, 2016, 17(2): 136-146.

@article{title="PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells",
author="Xu-feng Fu, Kun Yao, Xing Du, Yan Li, Xiu-yu Yang, Min Yu, Mei-zhang Li, Qing-hua Cui",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells
%A Xu-feng Fu
%A Kun Yao
%A Xing Du
%A Yan Li
%A Xiu-yu Yang
%A Min Yu
%A Mei-zhang Li
%A Qing-hua Cui
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 2
%P 136-146
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500158

T1 - PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells
A1 - Xu-feng Fu
A1 - Kun Yao
A1 - Xing Du
A1 - Yan Li
A1 - Xiu-yu Yang
A1 - Min Yu
A1 - Mei-zhang Li
A1 - Qing-hua Cui
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 2
SP - 136
EP - 146
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500158

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.


方法:以慢病毒质粒pBABE为载体构建了PGC-1α稳定表达的CH1 PGC-1α细胞株(PGC-1α),同时转染空质粒pBABE作为对照(PB),结合RNA干扰CH1 PGC-1α中PGC-1α的过表达(Si),测定了ATP和ROS水平。用流式细胞术检测了细胞周期和免疫印迹检测了CyclinB1/D1的表达,并进一步分别用寡霉素抑制PGC-1α细胞中的ATP生成,用H2O2处理细胞以增加外源ROS水平。然后检测ATP和ROS改变后,对CyclinB1/D1表达及细胞周期的影响,以明确ATP和ROS是否参与PGC-1α对细胞周期的调控作用。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Acín-Pérez, P.R., Fernández, S.P., Peleato, M.L., et al., 2008. Respiratory active mitochondrial supercomplexes. Mol. Cell, 32(4):529-539.

[2]Althoff, T., Mills, D.J., Popot, J.L., et al., 2011. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J., 30(22):4652-4664.

[3]Bertoli, C., Skotheim, J.M., Bruin, R.A., 2013. Control of cell cycle transcription during G1 and S phases. Nat. Rev. Mol. Cell Biol., 14(8):518-528.

[4]Cannon, B., Houstek, J., Nedergaard, J., 1998. Brown adipose tissue: more than an effector of thermogenesis Ann. NY Acad. Sci., 856:171-187.

[5]Chaturvedi, R.K., Beal, M.F., 2013. Mitochondrial diseases of the brain. Free Radical Biol. Med., 63:1-29.

[6]Chen, G., Dai, J., Tan, S., et al., 2014. MTERF1 regulates the oxidative phosphorylation activity and cell proliferation in HeLa cells. Acta Biochim. Biophys. Sin., 46(6):512-521.

[7]Chen, Q., Yin, G., Stewart, S., et al., 2010. Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia. Biochem. Biophys. Res. Commun., 397(4):656-660.

[8]Dalton, S., 2013. G1 compartmentalization and cell fate coordination. Cell, 155(1):13-14.

[9]Falk, M.J., Shen, L., Gonzalez, M., et al., 2015. Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Mol. Genet. Metab., 114(3):388-396.

[10]Hahm, E.R., Sakao, K., Singh, S.V., 2014. Honokiol activates reactive oxygen species-mediated cytoprotective autophagy in human prostate cancer cells. Prostate, 74(12):1209-1221.

[11]Lehman, J.J., Barger, P.M., Kovacs, A., et al., 2000. Peroxisome proliferator-activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis. J. Clin. Invest., 106(7):847-856.

[12]Lin, J., Handschin, C., Spiegelman, B.M., 2005. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab., 1(6):361-370.

[13]Löbrich, M., Jeggo, P.A., 2007. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat. Rev. Cancer, 7(11):861-869.

[14]Luckhart, S., Giulivi, C., Drexler, A.L., et al., 2013. Sustained activation of Akt elicits mitochondrial dysfunction to block Plasmodium falciparum infection in the mosquito host. PLoS Pathog., 9(2):e1003180.

[15]Malumbres, M., Barbacid, M., 2009. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer, 9(3):153-166.

[16]Marinho, H.S., Real, C., Cyrne, L., et al., 2014. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol., 2:535-562.

[17]McBride, H.M., Neuspiel, M., Wasiak, S., 2006. Mitochondria: more than just a powerhouse. Curr. Biol., 16(14):R551-R560.

[18]Meirhaeghe, A., Crowley, V., Lenaghan, C., et al., 2003. Characterization of the human, mouse and rat PGC1β (peroxisome-proliferator-activated receptor-γ co-activator 1β) gene in vitro and in vivo. Biochem. J., 373(Pt 1):155-165.

[19]Miraglia, F., Betti, L., Palego, L., et al., 2015. Parkinson’s disease and α-synucleinopathies: from arising pathways to therapeutic challenge. Cent. Nerv. Syst. Agents Med. Chem., 15(2):109-116.

[20]Pieczenik, S.R., Neustadt, J., 2007. Mitochondrial dysfunction and molecular pathways of disease. Exp. Mol. Pathol., 83(1):84-92.

[21]Rice, A.C., Ladd, A.C., Bennett, J.P., 2015. Postmortem Alzheimer’s disease hippocampi show oxidative phosphorylation gene expression opposite that of isolated pyramidal neurons. J. Alzheimer’s Dis., 45(4):1051-1059.

[22]Rohas, L.M., St-Pierre, J., Uldry, M., et al., 2007. A fundamental system of cellular energy homeostasis regulated by PGC-1α. PNAS, 104(19):7933-7938.

[23]Schick, V., Majores, M., Fassunke, J., et al., 2007. Mutational and expression analysis of CDK1, cyclinA2 and cyclinB1 in epilepsy-associated glioneuronal lesions. Neuropathol. Appl. Neurobiol., 33(2):152-162.

[24]Shiota, T., Traven, A., Lithgow, T., 2015. Mitochondrial biogenesis: cell-cycle-dependent investment in making mitochondria. Curr. Biol., 25(2):R78-R80.

[25]Valero, T., 2014. Mitochondrial biogenesis: pharmacological approaches. Curr. Pharm. Des., 20(35):5507-5509.

[26]Vartak, R., Porras, C.A., Bai, Y., 2013. Respiratory supercomplexes: structure, function and assembly. Protein Cell, 4(8):582-590.

[27]Vega, R.B., Huss, J.M., Kelly, D.P., 2000. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor α in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol. Cell. Biol., 20(5):1868-1876.

[28]Wallace, D.C., 2005. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet., 39(1):359-407.

[29]Weinberg, F., Chandel, N.S., 2009. Mitochondrial metabolism and cancer. Ann. NY Acad. Sci., 1177(1):66-73.

[30]Won, J.C., Park, J.Y., Kim, Y.M., et al., 2010. Peroxisome proliferator-activated receptor-γ coactivator 1-α overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity. Arterioscler. Thromb. Vasc. Biol., 30(2):290-297.

[31]Wood, Z.A., Poole, L.B., Karplus, P.A., 2003. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science, 300(5619):650-653.

[32]Wu, Z., Puigserver, P., Andersson, U., et al., 1999. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 98(1):115-124.

[33]Xiong, W., Jiao, Y., Huang, W., et al., 2012. Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells. Acta Biochim. Bioph. Sin., 44(4):347-358.

[34]Xu, H., Lyu, S., Xu, J., et al., 2015. Effect of lipopolysaccharide on the hemocyte apoptosis of Eriocheir sinensis. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 16(12):971-979.

[35]Zhang, Y., Ba, Y., Liu, C., et al., 2007. PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway. Cell Res., 17(4):363-373.

[36]List of electronic supplementary materials

[37]Fig. S1 Immunofluorescence picture of CyclinD1 and CyclinB1 in PB, PGC-1α, and Si cells

[38]Fig. S2 Mitochondrial content indicated by MitoTracker Green fluorescence (analyzed by flow cytometry)

[39]Fig. S3 Change of CyclinD1/B1 levels in CH1-PGC-1α after 24 h of antimycin A treatment

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE