title: Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells.
abstract: 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 inhibitor-oligomycin-treatment 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.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
authors.forename: Deyong
authors.initials: D
authors.lastname: Tan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D050259:Genes, Mitochondrial / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000378:metabolism; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D056744:Cyclin B1; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D009840:Oligomycins; D014475:Uncoupling Agents; D019938:Cyclin D1; D000255:Adenosine Triphosphate