The role of Topoisomerase 3 in mitochondrial DNA replication

• Main Authors: TSAI, HAN-ZEN, 蔡涵任
• Other Authors: HSIEH, TAO-SHIH
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/08197232829194792845

博士 === 國防醫學院 === 生命科學研究所 === 104 === Background: Mitochondria play important roles in providing metabolic energy and key metabolites for synthesis of cellular building blocks. Mitochondria have additional functions in other cellular processes, including programmed cell death and aging. A previous study revealed Drosophila mitochondrial topoisomerase III alpha (Top3α) contributes to the maintenance of the mitochondrial genome and male germ-line stem cells. However, the involvement of mitochondrial Top3α in the mitochondrion-mediated aging process remains unclear. We used both the M1L flies and mice model to study the function of Top3α protein that lacks the mitochondrial import sequence and is thus present in cell nuclei but not in mitochondria. The Drosophila model system to examine the role of mitochondrial Top3α in the aging of fruit flies. The mice model to points a role of Top3 in early embryogenesis development. Results: Here, we reported that M1L flies exhibit mitochondrial defects which affect the aging process. First, we observed that M1L flies have a shorter life span, which was correlated with a significant reduction in the mitochondrial DNA copy number, the mitochondrial membrane potential, and ATP content compared with those of both wildtype and transgene-rescued flies of the same age. Second, we performed a mobility assay and electron microscopic analysis to demonstrate that the locomotion defect and mitophagy of M1L flies were enhanced with age, as compared with the controls. We showed that the correlation between the mtDNA deletion level and aging in M1L flies resembles what was reported in mammalian systems. Finally, we observed that the M1L homozygous mutants are embryonic lethal at E8.5 day.