Abstract
Mitochondria are dynamic organelles that involved in ATP synthesis, calcium concentration regulations and apoptosis. Aberrant mitochondrial morphology caused by abnormal equivalence of fusion and fission in were found in neurodegenerative patients. The aim of my thesis is to study the regulation of mitochondria dynamics. In the first part, I focused on the protein that interacts with mitochondria fission Drp1 called CAP2 (cyclase associated protein 2). CAP2 is a highly conserved protein that plays critical roles in regulating acting dynamics and Ras/cAMP signaling pathway. I manipulated CAP2 expression levels by transfecting either overexpression vectors or RNAi and applied confocal microscope to monitor mitochondrial morphology. My experiments found that overexpression of CAP2 caused mitochondria fragmentation and inhibition of CAP2 lead to elongation. These results indicated that CAP2 does involved in regulating mitochondria dynamics. The second part of my thesis is focus on the effects of nature products on mitochondria dynamics. The dehydrated citrus peels used in traditional Chinese medicine contain the most common flavones: polymethoxylated flavones (PMFs). Both nobiletin and tangeretin are abundant PMFs in citrus peels. Many researches had demonstrated that PMF and 5-OH PMFs involved in anti-inflammatory, antioxidants, antithrombotic and anticarcinogenic processes and affected apoptosis. In my experiments, the survival rates of Hela cells treated with different concentrations of nobiletin, tangeretin, 5-OH nobiletin and 5-OH tangeretin were dosage dependent. In addition, 10 μM PMFs treatments altered mitochondrial dynsmics in HeLa cells. Our results of PMFs suggested these molecules may be therapeutically useful in treating the neurodegenerative disorders caused by mitochondrial fusion and fission regulation defects.