Mitochondrial Morphology and Functions Associated with Cellular Senescence in Saccharomyces cerevisiae

• Main Authors: Chang, Ko-Wei, 張可薇
• Other Authors: Chang, Chuang-Rung
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/60224349322909294663

碩士 === 國立清華大學 === 生物科技研究所 === 100 === Mitochondrial morphology is in a dynamic balance between the fission and fusion. In yeast, the major fission proteins are Dnm1p and Fis1p, while Fzo1p and Mgm1p are involved in fusion. The mitochondrial fission/fusion machineries are associated with the regulation of mitochondrial functions including: the regulation of ATP production, the level of reactive oxygen species (ROS), the influx and efflux of material in mitochondria, and the removal of defective mitochondria (mitophagy). Previous studies have demonstrated that the impaired mitochondrial function is closely related to neurodegenerative diseases. In addition, many neurodegenerative disorders are progressed with aging. However, the relationship between cellular senescence and mitochondrial dynamics remains obscure. In this thesis, we applied yeast replicative senescent model to clarify the correlation between cellular senescence and mitochondria dynamics. We found that majority of senescent cells have fragmented mitochondria. By using gene deletion strains in bioimaging analyses, we found that cellular senescence associated mitochondrial fragmentation depends on conventional mitochondrial fission proteins. In addition, we found that the senescent cells have higher mRNA level of fission genes. We then examined one of the potential causes of that the higher level of fission genes in replicative senescent cells. Our results also demonstrated that the mitochondrial DNA copy number increases in replicative senescent cells. Furthermore, mitochondria dynamics in chronological senescent cells was found to be distinct from replicative senescent cells. These results indicate that cellular senescence does have effects on mitochondria dynamics.