果蠅選擇性細胞自噬作用模式系統的建立與探討

Establishment of a selective autophagy model system in Drosophila melanogaster

鄭威廷(Wei-Ting Jheng)

指導教授 ： 陳光超

國立臺灣大學/生命科學院/生化科學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10015

摘要

細胞自噬是透過分解細胞內成分短暫彌補營養缺乏時的調控機制。除了隨機分解細胞內物質，細胞自噬也可以選擇性地消除特定胞器來調控其數量和完整性。粒線體吞噬作用(mitophagy)首先在酵母菌中被發現。Mitophagy是一種只特定吞噬粒腺體的細胞自噬作用。Mitophagy截至目前研究被發現與神經退化性疾病有關，如帕金森氏症或阿茨海默氏症均被發現有mitophagy的缺陷。在此次的研究結果，我們藉由對果蠅幼蟲施以CCCP(carbonyl cyanide 3-chlorophenylhydrazone) 或者粒線體complex I inhibitor rotenone兩種導致粒線體損傷的藥物來引發mitophagy。在添加CCCP或rotenone後，我們可以觀察到果蠅脂肪體(fat body)粒線體的損傷以及被吞噬的受損粒線體。此外，我們利用這個模型來檢驗先前經由我們實驗室發現的細胞自噬相關蛋白質Lack。當我們降低Lack表現量時可以抑制Atg1所導致的rough eye缺陷。而在果蠅的脂肪體中表達lack時，此蛋白亦能夠影響粒線體的形態以及吞噬粒線體的過程，但此機制仍須進一步研究與討論。

關鍵字

細胞自噬 ； 粒線體 ； 粒線體自噬作用 ； 選擇性自噬作用 ； 帕金森氏症

並列摘要

Autophagy is a cellular recycling pathway that can compensate for nutrient deprivation by degrading intracellular components. In addition to random degradation of cellular components, autophagy also selectively eliminates damaged proteins and organelles to promote cell survival. Mitophagy was first identified in yeast, and it is involved the elimination of mitochondria. Recent studies have shown that mitophagy may play a role in neurodegenerative disease, like Parkinson’s disease or Alzheimer’s disease. In our study, we establish a model system in Drosophila by treating flies with protonphore CCCP or complex I inhibitor rotenone to induce mitophagy. When treating animals with CCCP or rotenone, we observed mitochondrial damage and found that damaged mitochondria were engulfed by autophagosome. We recently identified Lack as a modifier of Atg1-induced rough eye phenotype. We further utilized the Drosophila mitophagy model to examine the role of Lack. Overexpression and knockdown of lack in larval fat body caused aberrant mitochondrial morphology. However, its role in mitophagy remains to be elucidated.

並列關鍵字

autophagy ； mitochondria ； mitophagy ； selective autophagy ； Parkinson’s disease

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