期刊
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
卷 44, 期 4, 页码 347-358出版社
OXFORD UNIV PRESS
DOI: 10.1093/abbs/gms006
关键词
mitochondrial DNA content; mitochondrial gene expression; mitochondrial membrane potential; adenosine triphosphate; cell cycle; cyclins
资金
- National Natural Science Foundation of China [30760057, 30960091, 31160237]
- Science & Technological Key Project of Yunnan Province [2008CC003, 2008CD069, 2011C1]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20115301120009]
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 dynamics and cell cycle progression remains to be clarified. To investigate the relationship between mitochondrial function and cell cycle regulation, the mitochondrial gene expression profile 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 starvation, 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 stimulated 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 cyclin D1 expression began to increase at 4 h after serum triggered cell cycle. ATP synthesis inhibitoroligomycintreatment suppressed the cyclin D1 and cyclin B1 expression levels and blocked cell cycle progression. Taken together, our results suggested that increased mitochondrial gene expression levels, oxidative phosphorylation activation, 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.
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