Studies on Drosophila genes related to cancer and their roles in cell metabolism

ショウジョウバエの癌関連遺伝子とその細胞代謝における役割についての研究

2015-03-25

2015-03-25

Mitochondria are cellular occupants which are referred as the power plant of the eukaryotes cells. They play important roles in producing adenosine triphosphate through the oxidative phosphorylation, maintaining the environment within our cells by control cytolysis calcium concentration. Mitochondrial dysfunction is reported in aging and many severe diseases such as neurodegenerative diseases, cancer. Although mitochondrial dysfunction is the energy production problem, the mechanisms of mitochondrial dysfunction in all cases are yet unclear. In my study, I focus on two of genes: SCO2 (synthesis of cytochrome c oxidase 2) which is associated to COX deficiency; and FUS (Fuses in Sarcoma) which is related to neurodegenerative diseases. In the first part, I investigate the in vivo role of SCOX (homologue of human SCO2 in Drosophila melanogaster) by generating the SCOX-knockdown flies and full-length SCOX transgenic flies. The results are that knockdown of SCOX in all cells to be associated with lethality in larvae or pupil while the full length SCOX transgenic flies showed a longer lifespan more than, correlated with the decrease and increase in ATP level, respectively. Finally, when cultured on paraquat-added medium, full length SCOX transgenic flies exhibited an elongated lifepan. I hypothesized that SCOX play an important role in ATP consumption and production. In the next part, I study on Caz-knockdown flies to investigate the in vivo roles of Cabeza (Caz, which is a FUS homologue in Drosophila melanogaster). The results indicated that Caz-knockdown induces apoptosis and inhibits differentiation of cone cells. Moreover, mutation of EGFR pathway-related genes suppressed the rough eye phenotype induced by Caz-knockdown and the rhomboid-1 mutation rescued the fushion of cone cells and ommatidia observed in Caz-knockdown flies. That suggests Caz negatively regulates the EGFR singalling pathway in Drosophila melanogaster. More in vivo and in vitro experiments will be done to clarify other genetic functions of SCOX and Caz, and the mechanism of mitochondrial dysfunction and neurodegenerative disorders can be clearly elucidated.

博士（学術）

京都工芸繊維大学

14303甲第734号

http://hdl.handle.net/10212/2254

en

ETD

Thesis or Dissertation

Thesis