Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells  

作　　者：Wei Xiong Yang Jiao Weiwei Huang Mingxing Ma Min Yu Qinghua Cui Deyong Tan 

机构地区：[1]Laboratory of Biochemistry and Molecular Biology,School of Life Sciences,Yurman University,Kunming 650091,China [2]Department of Biochemistry and Molecular Biology,School of Basic Medicine,Dali University,Dali 671000,China [3]Institute of Molecular and Clinical Medicine,Kunming Medical University,Kunming 650031,China [4]Institute of Medical Biology,Chinese Academy of Medical Sciences,Peking Union Medical College,Kunming 650118,China

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第4期347-358,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China （Nos. 30760057, 30960091, and 31160237）, Science ＆ Technological Key Project of Yunnan Province （Nos. 2008CC003, 2008CD069, and 2011C1）, and Specialized Research Fund for the Doctoral Program of Higher Education of China （No. 20115301120009）.

摘　　要：Human cervical cancer HeLa cells have functional mitochondria. Recent studies have suggested that mitochondrial metabolism plays an essential role in tumor cell proliferation. Nevertheless, how cells coordinate mitochondrial dy- namics and cell cycle progression remains to be clarified. To investigate the relationship between mitochondrial func- tion and cell cycle regulation, the mitochondrial gene ex- pression profde and cellular ATP levels were determined by cell cycle progress analysis in the present study. HeLa cells were synchronized in the G0/G1 phase by serum star- vation, and re-entered cell cycle by restoring serum culture, time course experiment was performed to analyze the expression of mitochondrial transcription regulators and mitochondrial genes, mitochondrial membrane potential （MMP）, cellular ATP levels, and cell cycle progression. The results showed that when arrested G0/G1 cells were stimu- lated in serum-containing medium, the amount of DNA and the expression levels of both mRNA and proteins in mitochondria started to increase at 2 h time point, whereas the MMP and ATP level elevated at 4 h. Furthermore, the cyelin D1 expression began to increase at 4 h after serum triggered cell cycle. ATP synthesis inhibitor-oligomycin-- treatment suppressed the cyclin D1 and cyclin B1 expres- sion levels and blocked cell cycle progression. Taken to- gether, our results suggested that increased mitochondrial gene expression levels, oxidative phosphorylation activa- tion, and cellular ATP content increase are important events for triggering cell cycle. Finally, we demonstrated that mitochondrial gene expression levels and cellular ATP content are tightly regulated and might play a central role in regulating cell proliferation.Human cervical cancer HeLa cells have functional mitochondria. Recent studies have suggested that mitochondrial metabolism plays an essential role in tumor cell proliferation. Nevertheless, how cells coordinate mitochondrial dy- namics and cell cycle progression remains to be clarified. To investigate the relationship between mitochondrial func- tion and cell cycle regulation, the mitochondrial gene ex- pression profde and cellular ATP levels were determined by cell cycle progress analysis in the present study. HeLa cells were synchronized in the G0/G1 phase by serum star- vation, and re-entered cell cycle by restoring serum culture, time course experiment was performed to analyze the expression of mitochondrial transcription regulators and mitochondrial genes, mitochondrial membrane potential （MMP）, cellular ATP levels, and cell cycle progression. The results showed that when arrested G0/G1 cells were stimu- lated in serum-containing medium, the amount of DNA and the expression levels of both mRNA and proteins in mitochondria started to increase at 2 h time point, whereas the MMP and ATP level elevated at 4 h. Furthermore, the cyelin D1 expression began to increase at 4 h after serum triggered cell cycle. ATP synthesis inhibitor-oligomycin-- treatment suppressed the cyclin D1 and cyclin B1 expres- sion levels and blocked cell cycle progression. Taken to- gether, our results suggested that increased mitochondrial gene expression levels, oxidative phosphorylation activa- tion, and cellular ATP content increase are important events for triggering cell cycle. Finally, we demonstrated that mitochondrial gene expression levels and cellular ATP content are tightly regulated and might play a central role in regulating cell proliferation.

关 键 词：mitochondrial DNA content mitochondrialgene expression mitochondrial membrane potential adenosine triphosphate cell cycle CYCLINS 

分 类 号：Q255[生物学—细胞生物学] Q253