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CLC number: Q25

On-line Access: 2018-06-04

Received: 2017-03-15

Revision Accepted: 2017-06-12

Crosschecked: 2018-05-14

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Citations:  Bibtex RefMan EndNote GB/T7714


Qing-hua Cui


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Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.6 P.415-424


PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS

Author(s):  Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui

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

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

Key Words:  B-cell lymphoma 2 (Bcl-2), Peroxisome proliferator-activated receptor-γ, co-activator 1α, (PGC-1α, ), Mitochondria, Reactive oxygen species (ROS), Cell cycle

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Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui. PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS[J]. Journal of Zhejiang University Science B, 2018, 19(6): 415-424.

@article{title="PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS",
author="Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS
%A Kun Yao
%A Xu-feng Fu
%A Xing Du
%A Yan Li
%A Shan-shan Yang
%A Min Yu
%A Qing-hua Cui
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 6
%P 415-424
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700148

T1 - PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS
A1 - Kun Yao
A1 - Xu-feng Fu
A1 - Xing Du
A1 - Yan Li
A1 - Shan-shan Yang
A1 - Min Yu
A1 - Qing-hua Cui
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 6
SP - 415
EP - 424
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700148

B-cell lymphoma 2 (Bcl-2) has a dual function, acting as both an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which it suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G0/G1 to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintain a significantly lower level of mitochondrial reactive oxygen species (ROS) than control cells. Based on the fact that ROS mediate cell cycle progression and are controlled by peroxisome proliferator-activated receptor-γ; co-activator 1α; (PGC-1α;), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1α might be related to the cell cycle function of Bcl-2. In this paper, we show that PGC-1α is upregulated by Bcl-2 overexpression and downregulated following Bcl-2 knockdown or downregulation after serum starvation. However, Bcl-2 is negatively regulated by PGC-1α expression. Further, co-immunoprecipitation (co-IP) experiments showed that PGC-1α protein is co-precipitated with Bcl-2 at the G0/G1 phase. Taken together, our results suggest that PGC-1α interacts with Bcl-2 after serum depletion, and that Bcl-2 might recruit PGC-1α to reduce ROS, which in turn delays cell cycle progression in coordination with Bcl-2.


目的:探究过氧化物酶体增生激活受体γ协同刺激因子1α (PGC-1α)和B细胞淋巴瘤-2(Bcl-2)在调控细胞周期中的相互关系.
方法:用蛋白质印迹法(Western blotting)检测了接触抑制和血清饥饿处理的NIH3T3过表达Bcl-2的细胞中PGC-1α的表达,并且分别检测了用Bcl-2和PGC-1α的小干扰RNA(siRNA)降低U251细胞(内源性高表达Bcl-2和PGC-1α)中的Bcl-2和PGC-1α的表达,最后用免疫共沉淀(co-IP)检测了二者的关系.

关键词:过氧化物酶体增生激活受体γ协同刺激因子1α (PGC-1α);B细胞淋巴瘤-2(Bcl-2);线粒体;活性氧自由基(ROS);细胞周期

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


[1]Aquilano K, Vigilanza P, Baldelli S, et al., 2010. Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J Biol Chem, 285(28):21590-21599.

[2]Bagattin A, Hugendubler L, Mueller E, 2010. Transcriptional coactivator PGC-1α promotes peroxisomal remodeling and biogenesis. Proc Natl Acad Sci USA, 107(47):20376-20381.

[3]Burdon RH, 1995. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Rad Biol Med, 18(4):775-794.

[4]Cheng N, Janumyan YM, Didion L, et al., 2004. Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival. Oncogene, 23(21):3770-3780.

[5]Du X, Fu XF, Yao K, et al., 2017. Bcl-2 delays cell cycle through mitochondrial ATP and ROS. Cell Cycle, 16(7):707-713.

[6]Fu XF, Yao K, Du X, et al., 2016. PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 17(2):136-146.

[7]Hansen JM, Go YM, Jones DP, 2006. Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Ann Rev Pharmacol Toxicol, 46(1):215-234.

[8]Hardwick JM, Soane L, 2013. Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol, 5(2):a008722.

[9]Heiden MGV, Cantley LC, Thompson CB, 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930):1029-1033.

[10]Hockenbery D, Nunez G, Milliman C, et al., 1990. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 348(6299):334-336.

[11]Janumyan YM, Sansam CG, Chattopadhyay A, et al., 2003. Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry. EMBO J, 22(20):5459-5470.

[12]Janumyan Y, Cui Q, Yan L, et al., 2008. G0 function of BCL2 and BCL-xL requires BAX, BAK, and p27 phosphorylation by Mirk, revealing a novel role of BAX and BAK in quiescence regulation. J Biol Chem, 283(49):34108-34120.

[13]Korsmeyer SJ, Shutter JR, Veis DJ, et al., 1993. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol, 4(6):327-332.

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

[15]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(1):155-165.

[16]Murphy KL, Kittrell FS, Gay JP, et al., 1999. Bcl-2 expression delays mammary tumor development in dimethylbenz(a) anthracene-treated transgenic mice. Oncogene, 18(47):6597-6604.

[17]Nunez G, Seto M, Seremetis S, et al., 1989. Growth- and tumor-promoting effects of deregulated BCL2 in human B-lymphoblastoid cells. Proc Natl Acad Sci USA, 86(12):4589-4593.

[18]Oltval ZN, Milliman CL, Korsmeyer SJ, 1993. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell, 74(4):609-619.

[19]Safdar A, Little JP, Stokl AJ, et al., 2011. Exercise increases mitochondrial PGC-1α content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem, 286(12):10605-10617.

[20]Smith BK, Mukai K, Lally JS, et al., 2013. AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor γ co-activator 1α translocation to subsarcolemmal mitochondria in skeletal muscle. J Physiol, 591(6):1551-1561.

[21]Susnow N, Zeng L, Margineantu D, et al., 2009. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol, 19(1):42-49.

[22]Tsujimoto Y, Finger LR, Yunis J, et al., 1984. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science, 226(4678):1097-1099.

[23]Tsujimoto Y, Cossman J, Jaffe E, et al., 1985. Involvement of the bcl-2 gene in human follicular lymphoma. Science, 228(4706):1440-1443.

[24]Vail ME, Pierce RH, Fausto N, 2001. Bcl-2 delays and alters hepatic carcinogenesis induced by transforming growth factor α. Cancer Res, 61(2):594-601.

[25]Ventura-Clapier R, Garnier A, Veksler V, 2008. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovasc Res, 79(2):208-217.

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

[27]Yoon JC, Puigserver P, Chen G, et al., 2001. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature, 413(6852):131-138.

[28]List of electronic supplementary materials

[29]Fig. S1 Immunofluorescence images of PGC-1α and Bcl-2 protein co-localization in NIH3T3 cells

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