Molecular mechanism studies of Mammalian sterile20-like protein kinase 3 in apoptosis and oxidative phosphorylation

• Main Authors: Lin, Chia-Ying, 林佳穎
• Other Authors: Yuan, Chiun-Jye
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/72353139987188179113

博士 === 國立交通大學 === 分子醫學與生物工程研究所 === 98 === Mammalian sterile-20 protein kinase 3 (Mst3) plays an essential role in the apoptotic and non-apoptotic pathway. Caspases are shown to be involved in the Mst3-mediated apoptosis, but the staurosporine-induced apoptosis is slightly suppressed by the caspase inhibitor, z-DEVD-fmk. Mst3 is though that Mst3 is not only involves in caspase-dependent but also in caspase-independent apoptotic pathway. The study demonstrates that Mst3 controls the mitochondrial integrity through the regulation of Bax and subsequently promote the nuclear translocation of caspase-independent proapoptotic members, apoptosis-inducing factor and endonuclease G from mitochondria in HeLa cells. Following, the nuclease activity associated with endonuclease G is modulated. Thus, Mst3 is inferred that the participation in staurosporine-induced apoptosis mediated its cellular localization of the intermembrane space of mitochondria. The bold is confirmed by co-immunofluorescent staining, transmission electron microscopic imaging and immuno-blotting after subcellular fractionation. Similar results are also observed in human trophoblast cell line 3A-sub-E cells, suggesting that the mitochondrial localization of Mst3 is a general phenomenon. The mitochondrial targeting segment of Mst3 is between residues 314-431. The intermembrane space-Mst3 regulate the respiratory transport chain complexes I and III and the dependence of glucose for ATP synthesis. The results indicate that Mst3 plays an important role not only in caspase dependent and independent- apoptotic pathway but also in oxidative phosphorylation.