The Effect of Mitochondrial Dynamics on Cell Cycle Progression
Chromosome duplication and segregation is the most critical event during cell cycle progression and appears to be precisely controlled by several defined machineries. On the other hand, the mechanisms by which cellular organelles duplicate and partition into two daughter cells during cell division have been barely studied. Here, we investigated how mitochondria duplicate and partition during cell cycle progression. Using cell synchronization techniques, different phases of cells in cell cycle were collected and analyzed for the changes in mitochondrial DNA copy number and mitochondrial mass. We found that mitochondria mass gradually increased from G1 phase to mitotic phase and reduced back at the returning G1 phase. However, mtTFA, NRF-1, PRC, known as transcriptional factors regulating mitochondria biogenesis, did not significantly change during cell cycle progression. Interestingly, we found that heterogeneous mitochondrial population such as tubular network and fragmented small mitochondria found in interphase no longer exist in mitotic cells, suggesting that the mitochondrial reorganization may occur during G2 to M transition. When expression levels of hFis1, Mfn and Drp1 regulating mitochondrial fusion and fission were compared during cell cycle progression, we found that Mfn1 was specifically increased at G2 phase. Finally, we established the HeLa cell lines overexpressing hFis, Mfn or Drp1 genes, which accompanied with elongated or fragmented mitochondria. Interestingly, we observed that HeLa cells overexpressing the dominant-negative mutant of Drp1 gene showed delayed cell cycle progression, especially at G2/M phase. We are currently investigating whether the alteration in mitochondrial dynamics affects cell cycle progression in mammalian cells.
세포 분열 주기, 미토콘드리아 biogenesis, 미토콘드리아 형태, G2->M 전이, Cell cycle, Mitochondria biogenesis, Mitochondrial dynamics, Delayed cell cycle progression
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