Summary: | 碩士 === 國立清華大學 === 生物科技研究所 === 103 === Mitochondria are dynamic organelles that continuously undergo fusion and fission. Mitochondrial dynamics is important for maintaining mitochondrial integrity and cellular function. Aging is a degenerative process that exhibit physiological and mitochondrial dysfunction. Previous studies of our lab revealed mitochondrial fragmentation was present in senescent yeast cells. Resveratrol, a polyphenol mitigated mitochondrial fragmentation and superoxide level. In addition, resveratrol elevated membrane potential in the senescent yeast cells. However, the mechanism of how resveratrol-mediated mitochondria in senescent yeast cells remains unclear. We aim to elucidate the potential mechanisms. Previous studies indicated resveratrol can ameliorate aging-related metabolic phenotypes via inhibiting phosphodiesterase activity. In this thesis, I applied biotin-streptavidin system to isolate replicative senescent yeast cells to clarify the effect of phosphodiesterase, Pde2 on mitochondria. My results demonstrated that deletion of PDE2 reverted the effects of resveratrol on mitochondria dynamics and showed different transcription level of fission/ fusion genes. In the mitochondrial activity assay, resveratrol did not mitigate the superoxide level in Δpde2 senescent cells. Those results indicated that Pde2 is required for resveratrol-mediated mitochondrial dynamics and superoxide scavenging. These evidences provide hints to elucidate resveratrol signaling pathway in the regulation of mitochondrial dynamics in cellular senescence.
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